JP4137998B2 - Powder coating composition for electrostatic coating of pharmaceutical substrates - Google Patents

Powder coating composition for electrostatic coating of pharmaceutical substrates Download PDF

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JP4137998B2
JP4137998B2 JP53386596A JP53386596A JP4137998B2 JP 4137998 B2 JP4137998 B2 JP 4137998B2 JP 53386596 A JP53386596 A JP 53386596A JP 53386596 A JP53386596 A JP 53386596A JP 4137998 B2 JP4137998 B2 JP 4137998B2
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JPH11505530A (en
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エドワード ホーガン，ジョン
ページ，トレバー
リーブス，リンダ
ニコラス スタニフォース，ジョン
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フオカス リミテッド
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
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    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
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    • A—HUMAN NECESSITIES
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    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2893—Tablet coating processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
    • B05B5/08—Plant for applying liquids or other fluent materials to objects
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
    • B05B5/08—Plant for applying liquids or other fluent materials to objects
    • B05B5/081—Plant for applying liquids or other fluent materials to objects specially adapted for treating particulate materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
    • B05B5/08—Plant for applying liquids or other fluent materials to objects
    • B05B5/082—Plant for applying liquids or other fluent materials to objects characterised by means for supporting, holding or conveying the objects
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05B—SPRAYING APPARATUS; ATOMISING APPARATUS; NOZZLES
    • B05B5/00—Electrostatic spraying apparatus; Spraying apparatus with means for charging the spray electrically; Apparatus for spraying liquids or other fluent materials by other electric means
    • B05B5/08—Plant for applying liquids or other fluent materials to objects
    • B05B5/087—Arrangements of electrodes, e.g. of charging, shielding, collecting electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B05—SPRAYING OR ATOMISING IN GENERAL; APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D—PROCESSES FOR APPLYING FLUENT MATERIALS TO SURFACES, IN GENERAL
    • B05D1/00—Processes for applying liquids or other fluent materials
    • B05D1/02—Processes for applying liquids or other fluent materials performed by spraying
    • B05D1/04—Processes for applying liquids or other fluent materials performed by spraying involving the use of an electrostatic field
    • B05D1/045—Processes for applying liquids or other fluent materials performed by spraying involving the use of an electrostatic field on non-conductive substrates
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Medical Preparation Storing Or Oral Administration Devices (AREA)
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  • Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
  • Electrostatic Spraying Apparatus (AREA)
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Abstract

A method of coating a pharmaceutical substrate, especially a tablet core, wherein a pharmaceutically acceptable powder coating material comprising active material is electrostatically applied to a surface of the substrate, wherein the coated substrate constitutes a dosage unit; and a powder coating material suitable for use in the electrostatic powder coating of a pharmaceutical substrate, in which the material is pharmaceutically acceptable, is treatable to form a film coating and includes composite particles, the composite particles comprising two or more components having different physical and/or chemical properties, the material comprising active material. The pharmaceutical substrate may contain the same active material as the powder coating material or may contain a different active material from the powder material or may contain no active material.

Description

本発明は、粉末塗装材料による医薬基材の静電塗装および医薬基材塗装用の粉末塗装材料に関するものである。特に、本発明は、粉末塗装材料による医薬錠剤芯の静電塗装および医薬錠剤芯塗装用の粉末塗装材料に関するものであるが、これに限定していない。明細書の全体にわたり医薬錠剤に言及し、且つ特に、本発明は従来形状の医薬錠剤に関する出願とみられがちであるが、この用語は、ペレット、カプセルや小球の如き経口摂取されるその他の製品も包含するような広範な意味で解釈すべきである。
金属物体のような導電性基材の静電塗装はよく知られるところである。例えば、ある種の塗料噴霧方法において、塗料を帯電させて、接地した金属物体上に塗料滴を噴霧する。この方法は、基材上に均一塗装膜を形成させる点で成功を収めている。
非電導性基材、特に医薬錠剤芯の静電塗装はかなり難しい。何年もの間、錠剤の静電塗装に関する提案が行われてきた。例えば、英国１０７５４０４号は錠剤塗装用の装置を提案しており、高ポテンシャル場で塗装溶液の微細粒子を噴霧器を用いて錠剤上に噴霧している。一例として赤外線ヒーターを用いて塗装を乾燥する。しかし、この提案は実質的に産業的な規模で実施されたことがなく、かつ医薬錠剤芯の塗装は、回転ドラム中で液体塗料を適用することにより、バッチ法で通常実施している。この液体塗装材料は、或る場合には勿論、粉末形態で供給されることもあるが、仮にそうであっても、その後に塗装材料は液体中に溶解または分散させて使用する。従って、塗装材料は粉末形態で錠剤芯に適用していない。
医薬錠剤芯に対して粉末塗装より液体塗装の適用が、多くの場合に容易である。錠剤に粉末を固着させることが難しく、且つ芯に塗装を固定するために、通常有機材料を含んでいる錠剤芯を傷めることなく、粉末を薄膜に変換する必要がある。さらに、均一塗装が要求され、錠剤芯上に均一な粉末塗装を得ることが難かしい。
液体塗装を使用する場合、塗装を乾燥する必要がある。理論上は、或る環境で乾燥を室温で実施可能であるが、しかしながら、工程を実施する速度の点から錠剤の加熱は産業の場では重要であり、且つ液体塗装に使用した溶剤を蒸発させるために必要なエネルギーの大量投入故に費用がかかる。液体塗装の他の欠点は、有用な液体、好適には水に溶解しない又は適切に分散しない材料は塗装材料に使用できない点である。
ＷＯ９２／１４４５１号は、医薬錠剤の静電粉末塗装に関するものであり、医薬錠剤芯を接地したコンベヤベルトにのせて移送し、静電的帯電粉末を芯に向けて噴霧して芯表面に固着した粉末塗装を形成させる方法を解説すると共に例証している。その後に、粉末塗料は溶融して芯に固定した溶融薄膜塗装を与える。
このような方法の欠点は、芯に向けて噴霧した粉末の大部分が帯電せず、芯上に沈積しないことである。このことは、噴霧飛沫と粉末材料の浪費に繋がり、且つ均一塗装の達成を困難にしている。
第１の観点では、本発明は、医薬錠剤芯の静電粉末塗装用に適した粉末塗装材料の提供を試み、且つ医薬錠剤芯の静電塗装方法を提供し、特殊粉末塗装材料の使用により静電塗装を容易にする試みを行う。
本発明の第１の観点は、錠剤芯の静電粉末塗装、特に以下に定義する塗装方法に用いるもので、且つこの方法に対する使用適性を与える特殊な特性を有する、粉末塗装材料を提供するものである。好ましくは、粉末塗装材料が有する前記の特殊な特性は以下に定義するもので、そしてこの特性により与えられる利点は採用する塗装方法の影響を受ける故、この方法もまた定義する。
本発明の第１の観点によれば、本発明は、医薬錠剤芯の静電粉末塗装に適する粉末塗装材料を提供するもので、前記材料は医薬的に許容でき、薄膜塗装加工ができ、且つ複合粒子を含み、前記複合粒子は異なった物理的及び／又は化学的特性を有する２またはそれ以上の成分から構成される。
粉末塗装材料が医薬的に許容できる材料であることは重要である。これは、それ自体が、粉末塗装材料に厳しい制約を課するもので、静電粉末塗装加工用として商業的に入手可能な少なくとも大部分の粉末塗装材料は生理学的に容認されず、且つ医薬錠剤芯の塗装材料として商業的に入手可能な材料は、その他の材料特性が不適切である理由により一般的に静電粉末塗装に向いていない。
本発明の粉末塗装材料は、少なくとも２種の異質な成分を含み、それぞれの異質な成分は異なる物理的及び／又は化学的特性を所有している。１成分材料の使用に比べ１成分以上から成る材料の使用により、前述のおよび明細書の何れかの箇所に記載する所望の特性を有する粉末材料の提供は、可なり容易になる。２またはそれ以上の異質な成分を含有する粉末材料に関して、粉末が数成分の複合粒子を含む場合に、改良塗装が達成されることを我々は見いだした。
用いる塗装方法が、例えば下記の実施例に記載されるような場合、１またはそれ以上の成分が芯上に塗装するために必要とする電気的特性を持たないならば、塗装材料粒子が１以上の成分を含有することは、特に重要となる。粒子が複合粒子でない場合、必要な電気的特性を有さない成分から成るこれらの粒子が、粉末供給源に単に止まることがあり、錠剤芯上に塗装されないであろう。
本明細書で使用する「複合粒子」の用語は、２またはそれ以上の異なる成分から形成される粒子を言う。この複合粒子は均質ではなく、複合粒子はそれぞれが異なる成分の微粒子から構成される２またはそれ以上の領域を有している。複合粒子は、個々別々の複合粒子形態であるか、或いは異なる成分の個々の粒子の集塊または凝集体であってもよく、集塊または凝集体は別々の複合粒子の挙動を示すものである。
有利な点として、少なくとも５０重量％の粉末粒子が複合粒子である。理想的なことをいえば、実質的に全ての粒子が複合粒子であればよいが、これは、特に複合粒子の粒子サイズが小さい場合、成し得ないことである。粉末が異なる物理的及び／又は化学的特性を有する２以上の成分を含む場合、好都合には、この複合粒子はその他の成分も含んでいる。理想的には、実質的に全ての複合粒子が、異質な成分のそれぞれを含む個々に分離した粒子から構成されることである。しかしながら、実際には、個々の成分粒子が凝集体または集塊として複合粒子を形成する場合に、満足な塗装が得られている。
好ましくは、２またはそれ以上の成分が同時処理される。この同時処理は、造粒、噴霧凝固、噴霧乾燥または同時粉砕から構成される。この同時処理が比較的大きいサイズを、例えば顆粒を、生むような結果となる場合、或る場合には引き続いて粉砕工程を行い、粒子サイズを減少させることが好都合である。新たに、微小化工程を実施してもよい。
周知の如く、粉末成分の混合により、通常は成分の均一な混合物が得られる。しかしながら、特殊な場合、混合条件、例えば成分の初期粒子サイズと混合手段を注意深く選択することにより、混合方法により複合粒子を得ることができる。
本発明の第１の観点に従えば、粉末塗装材料は、該材料を錠剤芯表面に塗装した後、処理して芯に固定された薄膜塗装を形成可能な材料である。このように、本発明の塗装方法は、錠剤芯表面を粉末で塗装後粉末を処理し錠剤芯表面に固定された薄膜塗装を形成する工程を含むものである。薄膜塗装は連続していることが好都合であり、この場合塗装は別々の部分に分割されていないが、しかし例えば処理工程中に互いに固定された塗装粒子間に、肉眼で認識不能な小間隙が存在している。このように、塗装は焼結したものである。或る用途では、薄膜塗装に間隙が存在しないか及び／又は実質的に均質であることが好ましい。
錠剤芯に初めに沈積した粉末材料は、多くの場合基材表面に単に弱く接着しているだけで、容易に取り除ける。しばしば錠剤芯自体の機械的強度が小さい故、医薬錠剤芯に塗装を行う場合に、薄膜塗装を形成するための処理は特に有利であり、そして強度付与のために薄膜塗装が使用され、塗装錠剤を包装や包装開封の如き次工程に更に耐えられるようする。薄膜塗装は錠剤芯に特別な強度を付与できるが、芯表面から分離したときにはしばしば大変に弱いものである。遊離薄膜としての薄膜塗装の抗張力は、例えば８ＭＮｍ-2またはそれ以下であり、そして塗装材料中のＴｉＯ2の量の増加に伴い抗張力が減少することが判明した。
遊離薄膜の抗張力が小さい場合、薄膜が、錠剤芯に対して優れた接着力をもち芯表面で凝集性の塗装となることが特に重要である。
粉末材料が薄膜塗装形成工程で液体相に変換される場合、該液体相中で粉末材料の粘度は５００パスカル以下、より好適には７５パスカル以下であることが好ましい。
粉末塗装材料が、薄膜塗装形成のために、２５０℃以下、より好適には２００℃以下の温度で処理可能であることは利点である。好都合なことに、粉末塗装材料が、大気圧下で２５０℃以下、より好適には２００℃以下の温度で溶融可能である。錠剤芯を傷めることなく粉末を処理して錠剤芯の周囲に塗装を形成することが重要であり、そしてこれは、有機材料を含有する多くの錠剤芯が熱に敏感である故、粉末材料に対し要求を課すことになる。粉末塗装材料は、好適には５０℃〜１８０℃の範囲、より好適には６０℃〜１００℃の範囲の融点を有する。ガラス転移を示す材料では、粉末塗装材料は好適には３０℃〜１８０℃の範囲の軟化点を有する。
上記の要件は粉末塗装材料に対し更なる制約を置くことになる。多くの材料は溶融せず、熱により炭化する。溶融性である他の材料と言えども、溶融のために熱源に長時間暴露する必要があり、それ故に芯に対し損傷を与える危険が相当に増大し、また芯上に薄膜を形成させる時間が経済的理由により容認しがたい。
粉末塗装材料が処理可能な所望温度は、当然のことながら錠剤芯を作成する材料により左右され、或る材料では処理工程が２５０℃を超える温度を含むこともあり得る。このような場合、そのような高温度への暴露時間は短縮される。
好ましくは、薄膜塗装を形成する粉末処理は、加熱工程、好適には赤外線輻射を用いた加熱工程を含み、しかも他の形態として電磁放射、電磁伝導、または電磁誘導を使用できる。粉末材料の処理は錠剤芯の周囲の圧力を部分的または全体に減圧して行うことができる。処理中の粉末材料の変化は、固体から液体へ、そして冷却により連続的固体薄膜への単純な物理的変化である。最近では、粉末材料は、処理中に硬化できるポリマー、例えばγ線、紫外線または無線周波帯のエネルギー照射により硬化して架橋ポリマー薄膜を形成するポリマーを含むことができる。
粉末塗装材料の粒子サイズが、静電粉末塗装法における材料の挙動に特に重要な影響を与えることを我々は発見した。材料の粒子サイズは小さいほうが有利である。少なくとも９５数量％且つ少なくとも９０容量％の粉末材料粒子が、５０μｍ以下の粒子サイズを有することが好ましい。「粒子サイズ」の用語は、粒子の相当する粒子直径を言い、例えばレザー光回折を用い測定できる。
関連粒子が、粒子の集塊または凝集体を含む複合粒子の場合、粒子サイズは複合粒子のサイズであり集塊または凝集体中の個々の粒子のサイズではない。
このような粒子サイズは、医薬錠剤芯用の塗装材料としては驚異的に小さく、事実このような小粒子サイズは、その凝集性の為に材料の製造や取扱を難しくする欠点を有するものと認識されている。しかしながら、静電塗装方法による医薬錠剤芯の塗装では、小粒子サイズの採用に特別な利点があり、欠点を取消して更に利点があることを、我々は発見した。例えば、小粒子により提供される、表面対質量の高比率は、粒子上の静電気力を慣性力に比較して増大させる。
静電気力の増大は粒子上の力を増大させる利点をもち、これが粒子を移動させて錠剤芯に接触させ、一方慣性力の減少は粒子を加速するに必要な力を減少させ且つ芯で後方に跳ね返り錠剤芯に到達する粒子の可能性を減少させる。少なくとも９０容量％の粉末材料の粒子が２０μｍ以下の粒子サイズを有する場合に、特に有利であることを我々は発見した。好ましくは、少なくとも９５数量％の粉末材料の粒子が３０μｍ以下の粒子サイズを有する。
特に、選ばれた粉末材料に関し、粒子が錠剤芯の表面から跳ね返る傾向が認められた場合、錠剤芯の表面に前処理組成物を適用した後に、錠剤芯を粉末材料供給源に近接して保持させる。前処理組成物は、芯表面による粒子捕捉を改善でき、７５０μｍもの大きさの大粒子を塗装材料として使用を可能にすることができた。前処理組成物に、液体が使用でき、粒子に作用する力を増し粒子を芯上に保持させる。前処理を採用する場合は、好適には少なくとも９０数量％の粒子が、３００μｍ以下のサイズであり、好適には少なくとも５０数量％の粒子が、２００μｍ以下のサイズである。
粒子サイズが極めて小さくなった場合、粉末の取扱に関する困難さは厳しくなる。従って、少なくとも５０容量％、好適には少なくとも７５容量％、最適には９０容量％の粉末が、少なくとも５μｍの粒子サイズを有することが、好都合である。
１つの好ましい粉末塗装材料において、平均粒子直径は約１０μｍであり、実質的に１００μｍより大なる直径を有する粒子を含んでいない。
好適には、少なくとも３０容量％の粉末粒子が、５μｍ〜２５μｍの範囲の粒子サイズを有している。
粉末粒子が狭い範囲の粒子サイズをもつことが、また特に重要であることを我我は発見した。好適には少なくとも３０重量％、より好適には少なくとも７５重量％の粒子が、ｘ〜２ｘの範囲、より好適にはｘ〜１．５ｘの範囲、最適にはｘ〜１．２５ｘの範囲にある粒子サイズを有し、但しｘは粉末の粒子サイズを表すものである。
例えば、比較的小サイズの粒子を有する粉末では、好適には少なくとも３０重量％の粒子が、１０μｍ〜２０μｍの範囲、より好適には１０μｍ〜１５μｍの範囲、最適には１０μｍ〜１２．５μｍの範囲にある粒子サイズを有する。
粒子が比較的大きい場合で、例えば前記のように前処理を行うならば、粒子サイズの好ましい相対的ばらつきは、相対的に小サイズの粒子に対するより通常小さくなる。
粉末の良好な均一塗布を、錠剤芯に、そして芯から芯へ実施するに関して、粒子サイズの範囲が大きい粉末は、粒子サイズの範囲が小さい粉末に比較して不利になることを、我々は見いだした。これは、或る粒子サイズを有する粒子が、より小さい又はより大きいサイズの粒子と比較したとき、錠剤芯上に優先的に塗装される故であると思考される。このことは、新規に仕立てたバッチの粉末材料で塗装した１つの塗装芯と、同一バッチで比較的あとで塗装した別の塗装芯で、芯の塗装の質の違い及び塗装の質の変化に繋がるものである。
粉末塗装材料が、粉末塗装材料の重量を基準にして１０重量％より多くない、好適には５重量％以下、より好適には３重量％より多くない水分量（乾燥時の水分損失により測定）を有することが好都合である。
幾つかの異なる静電気効果があり、本発明の第１の観点に従って、粉末を用い医薬錠剤芯を塗装する静電塗装方法でも使用でき、そして異なる効果の利用に特に適合した幾つかの異なる粉末の電気的特性がある。３つの異なる効果と粉末の関連特性をここで説明し、各々が他から独立し又は他の１またはそれ以上と関連して使用できることが評価されるに違いない。
第１の可能性は、粉末の粒子中に一時的双極子を誘導することであり、その後に双極子と、粉末の供給源および錠剤芯間の領域の電場との相互作用により粒子が錠剤芯の方向に導かれる。好ましくは塗装材料は１０8〜１０16Ωｍの範囲の固有抵抗を持っている。
第２の可能性は、粉末の粒子に正味電荷を適用することである。この正味電荷は、摩擦帯電的にまたはコロナ帯電により導入される。それ故に、塗装材料はこのような正味電荷に対し好ましくは受容性であり、電荷を保持（材料を錠剤芯上に十分導く程度に長く）できる。
第３の可能性は、粉末の粒子に永久双極子、または半永久双極子を与える事である。このような「エレクトレット」は、粉末供給源と錠剤芯間の領域に働く電界との相互作用により錠剤芯の方向に導かれるであろう。このように、塗装材料はエレクトレットを含んでもよい。
第４の可能性は、鉄または他の磁性材料又は常磁性材料を用いた粉末材料中に磁気双極子を与えることである。
粉末材料に適用された全体的な正味電荷に依存することなく、および粉末材料中の永久的な植えつけ電荷に依存することなく、粉末材料が錠剤芯に向かうことができるのは好ましい。このように、粉末材料が静電気力の作用下で移動に敏感であることは好ましく、その感度は以下に明示する試験により測られる。
粉末材料が静電気力の作用下で移動に敏感であるか否かを測るには、以下の試験を行う。
０．５ｇの粉末材料の試料を採り、これを６５％より大きくない相対湿度の環境中で接地電位に保ち水平に配置した導電性金属板上に置く。この粉末材料を単分子層に近い厚さに拡げる。粉末材料をその状態に３０分間放置した後、導電性の直径５ｍｍの丸い金属探針を粉末材料の中心の上方１０ｍｍに置き、高電圧を最初＋１０ＫＶ、次に−１０ＫＶ（電流は約５μＡに制限）で約１０秒間探針に適用する。全体としての材料を代表する粉末材料の粒子が、どちらか一方の高電圧適用中に、上方に引き寄せられて探針に接触すれば、その試験結果は、粉末材料が静電気力の作用下で移動に敏感であることになる。粉末材料の粒子が、上方に引き寄せられず探針に接触しない場合、または或る種の粒子だけが引き寄せられ、その引き寄せられた粒子が全体として材料を代表していないならば、試験結果は、粉末材料が静電気力の作用下で移動に敏感でないことになる。
粉末材料の感度は、当然、粉末の電気的特性と他の物理的特性、例えば粉末の粒子サイズとの組み合わせに依存する。
塗装材料の粒子が帯電（例えば、摩擦帯電的に）して芯表面に付着するには、粒子が実質的に全て同一記号の電荷になることが、特に好都合である。一群の粒子がプラスとマイナスの電荷の混合物を含む場合、不満足な塗装が芯表面に生成することが判った。粉末を荷電する場合、全粉末が実質的に同一記号の電荷となるような組成物から粉末が構成されることが好ましい。さらに、粒子が同一記号の電荷でない場合、粉末材料が過剰噴霧され塗装工程の効率を低下させる。また、殆どの粒子が実質的に同じ大きさの電荷をもつことが好ましい。
材料は１成分以上から成る故、成分の相対的割合を調節することにより、粉末材料の特性を変更できる。一般に、粉末材料の特性に言及する場合、その特性は、全体としての材料で示される特性であり、材料の１つまたはそれ以上の成分が単独でその特性を示すことはないと言うことである。しかし、全体としての粉末塗装材料ではなく、粉末塗装材料の１つ又は数種の成分が、下記の特性を示す場合には、それは満足すべきものとなる：例えば、低温度で薄膜塗装を形成する材料の長所が、その特性を示す材料の２つ又はそれ以上の成分中の唯一の成分によって、達成される；他の成分が固体粒子のままであり、薄膜塗装に変換する粒子に比べより大なる重量割合を表す；このような場合、２つの成分の粒子サイズに実質的なバラツキがある；例えば、薄膜塗装に変換された粒子は、５〜２０μｍの範囲の粒子サイズを有し、一方固体粒子として残る粒子は実質的により大きくなる。
異質な成分の１つが、粉末材料に必要な静電的特性を与える働きをすることがある。例えば、１つの異質な成分が、摩擦帯電的に及び／又はコロナ帯電的に帯電され、及び／又はエレクトレットまたは磁石となり、及び／又は、ここに記載する試験で定めるように、静電気力の作用下で移動に敏感になることがある。
粉末材料の化学的特性は、塗装を形成する効率と外観に重要である。
材料の化学的特性を論じるとき、複数の成分から成る材料を処理することが好都合であり、以下の議論で明らかにされるように、同一化合物が１つ以上の成分として使用され、それ故に粉末材料が２つ以上の成分から成ることに関する以下の記述中の言及は、成分が異なっているものと特に見なす場合を除き、２つ以上の異質な成分が必然的に存在することを要求しているとは見なすべきではない。
粉末材料が、好ましくは２５０℃以下の温度で、より好ましくは２００℃以下の温度で溶融して芯表面に連続薄膜を形成できる、第１成分を含むことが好ましい。上で議論したように、溶融は、上記温度範囲内で第１成分の融解、軟化または架橋の形態をとることができる。
第１成分が水性媒体に対し実質的に可溶性であることが好ましい。通常、第１成分は、中性の水性媒体に対して可溶性であり、選定されたＰＨ範囲、例えばＰＨ３〜ＰＨ６、またはＰＨ８〜ＰＨ１４にのみ溶解する。
好ましくは、第１成分は、ポリオキシエチレン、糖アルコール、と不飽和または飽和脂肪酸とエステルの１またはそれ以上から成る。第１成分は、２５０℃以下の温度で溶融するセルロース誘導体、例えばヒドロキシプロピルセルロースを含むことができる。全てのセルロース誘導体が第１成分として使用できるのではなく、例えばヒドロキシプロピルメチルセルロースは要求される溶融特性をもたず、且つ加熱により炭化する。
第１成分は、ポリエチレングリコールを含むことができ、該グリコールは良好な溶融特性をもち、且つ処理後、基材表面に良好な連続薄膜を形成できる。
好適な糖アルコールは、キシリトールであり、この材料は適切な電気的特性を有し、且つ適切な温度で融解して医薬錠剤芯の塗装における塗装材料として有用である。
その他の第１成分として使用可能な材料は、ワックスとオイル、ワックスまたはオイルのアルコール、ポロクサマー、アルキルナフタレン、例えばジエチルフタレート、クエン酸とエステルを含む。前記粉末の成分が液体の場合、成分を液体形態で単純に他の成分に添加でき、また、例えば粉末形態の担体材料と共に提供してもよい。
適切な溶融特性をもつ他の化合物が存在してもよく、上記は単に例示に過ぎない。
第１成分は、正に１つの化合物から成ることもあれば、２つまたはそれ以上の化合物を含んでもよい。
多くの場合、最も望ましい溶融特性を有する成分が、最適の電気的特性を備えていないし、及び／又は塗装の望ましい仕上がり、被覆または外観を提供しないものである。従って、上記の如く必要な電気的特性を有する第２成分を用いることが好ましい。
しかし、第１成分が、第２成分の所望する電気的特性を持ってもよく、また第２成分が、第１成分の所望する溶融特性を持ってもよいことは、理解すべきである。
第２成分は、アクリル酸、アクリル酸のポリマーとコポリマーおよびその誘導体、例えばポリメチルアクリレート、ポリアルケンとその誘導体、エステルを含み、アリールエステルとその誘導体、ポリビニルアルコールとエステル、セルロースとその誘導体、例えばセルロースエーテルとセルロースエステル（架橋型または非架橋型）、例えばエチルセルロース等の１つまたはそれ以上、１つまたはそれ以上の腸溶性ポリマー、例えばセルロースアセテートフタレートおよびヒドロキシプロピルメチルセルロースフタレートから成る。第２成分は、１つ又はそれ以上の生分解性ポリマー、例えばポリラクチド、ポリグリコリド、ポリヒドロキシブチレート、ポリヒドロキシバレレート、エチレンビニルアセテートコポリマー、とポリ酸無水物（ホモまたはヘテロポリマー）の１つ又はそれ以上を含んでもよい。第２成分は、ポリエチレンオキシドでもよい。
既に述べたように、第１成分と第２成分が同一化合物を含む可能性があるが、多くの場合は第１と第２成分は異質な化合物である。例えば、第１と第２成分が、それぞれキシリトールを含んでもよいが、しかしこの場合には、粘度調節剤と結晶化抑制剤を添加して第２成分に所望の溶融特性を与えるべきである。
２つまたはそれ以上の異質な成分を含む塗装材料は、異質な成分の分散を改善する分散剤成分を含むことが好ましい。分散剤成分は、好適にはアニオン性、カチオン性またはノニオン性の界面活性剤であり、しかし通常界面活性剤と呼ばれないが同様な効果を有する他の化合物でもよい。分散剤成分は、共溶剤であってもよい。
分散剤成分は、例えば、ラウリル硫酸ナトリウム、ドキュセイトソジウム、トゥイーン（ソルビタン脂肪酸エステル）、ポロクサマー、とセトステアリルアルコールの１つ又はそれ以上でもよい。第１及び／又は第２成分の化合物のように、分散剤成分は同一化合物を含んでもよい。上記の如く、第３と第１成分が共にポロクサマーを含んでもよい。材料が、材料の重量を基準にして、少なくとも１重量％、好適には２〜５重量％の分散剤成分を含むことが好ましい。
粉末塗装材料が減摩成分を含み、粉末塗装材料粒子間の摩擦力及び／又はその他の力を減少させ、粉末の流動性を改善することは、好都合である。減摩成分は、二酸化チタン、コロイダルシリカ、タルクまたは澱粉、またはそれらの混合物などがある。
塗装材料を「即時」放出型錠剤に用いるとき、粉末塗装材料が、塗装を破壊し得る崩壊剤を含むことが好都合である。錠剤芯上の塗装の場合、塗装中に崩壊剤の含有は、錠剤が摂取されたときに直ちに塗装の崩壊を促進する。
崩壊剤は、水分と接触したとき急速に且つ強力に膨潤するものであり、それにより塗装を破壊する。或る崩壊剤は、膨潤して数秒以内に元の容積の４０倍になる。適切な崩壊剤の例は、澱粉グリコール酸ナトリウム塩（架橋型）とカルボキシメチルセルロースナトリウム塩（架橋型）がある。
替わりに、または加えて、崩壊剤はウイッキング型でもよく、この型は塗装を通して錠剤芯へと水分浸透させるが、錠剤芯から塗装を通して水分の逆行を防ぎ、それによって塗装を破壊させる。ウイッキング型の適切な崩壊剤の例は、天然の澱粉、架橋型ポリビニルピロリドン（クロスプロビドン）がある。
崩壊剤は、ガス発生型、例えば炭酸ナトリウム、炭酸水素ナトリウムとソジウムグリシネートでもよい。
好適には、粉末塗装材料は１０容量％以下の崩壊剤を含有する。好ましくは、粉末は、５重量％以下、好適には２重量％以下、より好適には１重量％以下、最適には約０．５重量％の崩壊剤を含有する。
好ましくは、粉末塗装材料は、１またはそれ以上の不透明化剤、例えば二酸化チタンとタルクをさらに含有する。好ましくは、材料は、材料の重量を基準にして５０重量％以下、好適には４０重量％以下、より好適には３０重量％以下、最適には約１０重量％以下の不透明化剤を含む。
好ましくは、粉末塗装材料は、さらに１またはそれ以上の着色剤、例えば金属酸化物またはレーキ、例えばアルミニウムレーキ、酸化鉄、染料を含み、１またはそれ以上の味覚調節剤、例えばアスパルテーム、アセサルフェイムｋ、シクラミン酸塩、サッカリン、砂糖、及び糖アルコールまたは風味剤等を含むことができる。好ましくは、材料は、材料の重量を基準にして、１０重量％以下、好適には１〜５重量％の着色剤を含み、そして材料の重量を基準にして、好適には５重量％以下、より好適には１重量％以下の風味剤を含む。風味剤が甘味料の場合には、好ましくは、材料は０．５重量％以下の甘味料を含む。好ましくは、材料は、材料の重量を基準にして、５重量％以下の着色剤と風味剤を含む。減摩成分、不透明化剤、着色剤および味覚調節剤は、粉末塗装材料の他成分化合物と同一の化合物であってもよいと認められる。
粉末塗装材料は生物活性材料を含有することができ、これは生物学的環境で工程速度を増減する材料である。生物活性材料は、生理学的に活性な材料であればよい。活性材料を含有する塗装材料は、例えば同一または異質の活性材料を含む錠剤芯に適用でき、または非活性材料含有錠剤芯に適用できる。活性材料は、１またはそれ以上の化合物を含有するできる。活性材料は、酸消化・運動誘導剤、緩下剤、制痢剤、結腸・直腸薬、膵臓酵素と胆汁酸、抗不整脈薬、抗狭心症薬、利尿剤、抗高血圧薬、抗凝固薬、抗血栓薬、フィブリン溶解薬、止血薬、脂肪欠乏症薬、抗貧血・好中球減少病薬、催眠薬、抗不安薬、抗精神病薬、抗うつ薬、制吐薬、鎮痙薬、ＣＮＳ刺激薬、鎮痛薬、解熱薬、抗片頭痛薬、非ステロイド性抗炎症薬、抗通風薬、筋弛緩薬、神経筋薬、ステロイド、低血糖症薬、高血糖症薬、診断薬、抗生物質、抗真菌性薬、抗マラリヤ薬、抗ウイルス薬、免疫抑制薬、栄養薬、ビタミン、電解質、食欲抑制剤、欲求抑制剤、気管支拡張薬、去痰薬、鎮咳薬、粘液溶解薬、うつ血除去薬、抗緑内障薬、経口避妊薬、及び／又は抗腫瘍性薬を含む。
粉末塗装材料を適用する錠剤芯は、通常１またはそれ以上の不活性薬品を含んでいる。不活性薬品は、希釈剤、例えば乳糖、蔗糖、ブドウ糖、澱粉、セルロース、微晶質セルロース；結合剤、例えばポリビニルピロリドン、澱粉粘液、ゼラチン、アラビアゴム；崩壊剤、例えば架橋型カルボキシメチルセルロースナトリウム塩、澱粉グリコール酸ナトリウム塩、架橋型ポリビニルピロリドン；潤滑剤、例えばステアリン酸マグネシウム、フマル酸ナトリウムステアリル；グライダント、例えばコロイダルシリカ、タルク；界面活性剤、例えば湿潤剤で、ラウリル硫酸ナトリウム、ドキュセートナトリウム；着色剤；風味剤及び／又はガス発生剤、例えば重炭酸ナトリウムとクエン酸を含むことができる。
錠剤芯は、また上に掲載した１またはそれ以上の活性材料を含むことができる。好ましくは、粉末塗装材料は、粉末塗装材料の重量を基準にして、少なくとも０．５重量％、より好適には１重量％の活性材料を含む。例えば、錠剤上の１０ｍｇの塗装は、概略少なくとも０．０５ｍｇの活性材料を含有できる。
粉末塗装材料の成分を混合する割合は、粉末塗装材料を構成する材料と塗装する基材の性質に大きく依存する。所望の電気的および溶融特性が得られるように割合を調整する。通常、粉末塗装材料は、少なくとも１０重量％、好適には少なくとも１５重量％、最適には約２０重量％の第１成分を含有する。通常、粉末塗装材料は、少なくとも１０重量％、好適には少なくとも２０重量％、そしてより好適には少なくとも４０重量％の第２成分を含有し、それぞれ場合、粉末塗装材料の重量を基準にした。好ましくは、第２成分と第１成分の重量比率は、約３：１である。成分比率は、第１と第２成分を構成する材料に依存する。その比率は２：１または１：１である。
本発明は、さらに医薬基材の静電塗装用塗装材料を提供するもので、該塗装材料は活性材料を含有する。上に示した如く、活性材料を含む塗装材料は、例えば同一または異質の活性材料を含む錠剤芯に適用され、または非活性材料を含む芯に適用される。
活性材料の極少量摂取を錠剤形態で管理しようと試みる場合、活性材料を大量の非活性「充填」材料と混合して、管理可能サイズの錠剤を作成する。従来、活性材料と充填材料を単純に一緒に混合し、得られた混合物の摂取量を錠剤化していた。各錠剤中に含有される活性材料量の正確な管理が難しく、摂取量の均一性が不十分であることが判っていた。これは、特に、各錠剤が要求する活性材料量が少量の場合に認められた。
錠剤表面に活性材料を適用することにより、極少量の活性材料を正確に錠剤に適用でき、摂取量の再現性を改善できることが判明した。
塗装材料に含有される活性材料の量は、勿論、基材に適用される活性材料の摂取量の大小および形成される塗装の厚みに依存する。通常、材料は、塗装の重量を基準にして、少なくとも０．５重量％の活性材料を含有する。
塗装材料が、粉末塗装材料であることが好都合である。それ故、上に述べた方法と同様な方法を用いて塗装材料を適用することが便利であり、塗装材料は基材に対し正確に且つ過剰噴霧もなく適用される。
好ましくは、活性材料を含有する塗装材料は、５０μｍより大きくない粒子サイズを有する少なくとも９０数量％の粒子を含有する。好ましくは、少なくとも９０数量％の粉末粒子が、３０μｍ以下、より好ましくは２０μｍ以下の粒子サイズを有する。
また、本発明は、基材の静電塗装、特に医薬錠剤芯の静電塗装において、活性材料を含む塗装材料の使用を提供する。
また、本発明の第１の観点は、粉末材料で医薬錠剤芯を静電塗装する方法、と上に定義した粉末材料を提供する。
さらに、本発明の第１の観点は、基材の静電塗装用粉末塗装材料を提供し、粉末は上記の如き方法で得られる。
なお、さらに、本発明の第１の観点は、錠剤芯および上に定義したような粉末塗装材料を含む医薬錠剤を提供する。
さらに、本発明の第１の観点は、医薬錠剤芯を粉末で塗装する方法を提供し、該方法は、電界中で粉末塗装材料の供給源に近接して錠剤芯を保持し、且つ少なくとも芯の部分を塗装材料の電位と異なる電位に保持して、電位差を適用して粉末を粉末供給源から錠剤芯および芯表面の方向に導き、粉末塗装材料で塗装することを特徴としている。
錠剤芯の塗装は、電界の適用及び少なくとも錠剤芯の部分と粉末材料間の電位差の結果として、粉末材料を錠剤芯に向けて誘導する故、粉末材料の到達地点は、少なくとも最初のうちは錠剤芯の表面に制限される。若し、それが露出表面にだけ配列されるなら、それは粉末材料の近傍であり粉末材料に対し適切な電位差がある場所である。
本方法の特別な進歩は、連続工程で実施できることである。
錠剤芯を、粉末塗装材料の供給源に近接する領域を通る移送手段により移送することが、好都合である。錠剤芯を移送することにより、塗装工程の全般を通して錠剤芯を穏やかに取扱い、壊れやすい錠剤芯でさえも損傷しないことを保証できる。
本方法は、壊れやすく従来の錠剤塗装方法に耐えられない錠剤芯の塗装に使用できる。このように、本発明は、従来の形状をもち且つ広範囲の組成をもつ錠剤の製造を可能にした。また、従来にない形状の錠剤、例えば従来の円形面ではない、むしろ反対の平面をもつ錠剤も本発明の方法で製造できる。このような平面の錠剤は通常非常に壊れやすくて従来法では塗装できなかった。さらに、平面の錠剤はしばしば一緒に繋がり双子の錠剤や錠剤群を形成し、従来の塗装方法では適正に塗装できなかった。
錠剤芯が、粉末塗装材料供給源に近接する上手から保持され、そして粉末が、供給源上方から基材下部表面に移動する。
上に明示した塗装方法で作成した錠剤芯は単に一部分を塗装したものであり、本塗装方法は更なる次の工程を含み、該工程は、電界中で粉末塗装材料供給源に近接して塗装錠剤芯を保持し、錠剤芯の少なくとも一部分を塗装材料の電位と異なる電位に維持し、電位差の適用により粉末を、粉末供給源から錠剤芯に向けて誘導し、そして錠剤芯の非塗装面を粉末塗装材料で塗装するものである。このよにして、錠剤芯の全表面に容易に塗装を施すことが可能であり、また錠剤芯の異なる部分を異質の塗装材料で塗装することも可能である。例えば、錠剤の各反対面に色の異なる塗装を行うことができる。
さらに、本発明の第１の観点は、上に明示した方法によって静電塗装を施した医薬錠剤を提供するものである。
本発明の第１の観点に従い、特に医薬錠剤芯塗装のために、および塗装の適用から材料に課せられえる過酷な条件に対処するために、粉末塗装材料および塗装方法を開発した。医薬錠剤芯塗装に適した材料と方法を開発したが、我々は、さらに本材料および方法が有効に使用できる他の用途に思考を拡げた。例えば、医薬産業界で、本材料および方法は、経口摂取されないその他医薬製品の塗装に使用可能であり、例えば、ペッサリー、ブージーまたは座薬、または他の医薬基材に使用可能である。
本発明の第２の観点によれば、医薬基材の静電粉末塗装用粉末塗装材料が提供され、該材料は１またはそれ以上の下記の特性を有している。
ａ）人間及び／又は動物の食用に適する、
ｂ）少なくとも２つの異質な成分から成り、好ましくは粒子は複合粒子から成る、
ｃ）大気圧で２５０℃以下の温度で溶融して薄膜塗装を形成する、
ｄ）少なくとも３０重量％の粒子が５μｍ〜２０μｍの範囲の粒子サイズを有する、
ｅ）静電気力の作用の下で移動に敏感であり、ここに明示する試験法によりその感度を測定する。
粉末塗装材料が生理学的に許容できる材料であり且つ好適には医薬的に容認できる材料であることが、特に好ましい。本材料は、医薬錠剤芯塗装用材料に関する説明において前記したその他の特性を有することができる。
また、本発明は、基材の静電塗装用の少なくとも２つの異質な成分を含む粉末塗装材料を製造する方法を提供し、本方法は該少なくとも２つの異質な成分を同時処理する工程を含むものである。
さらに、本発明の第２の観点は、上に明示した粉末塗装材料により医薬基材を静電塗装する方法を提供する。
ここで、特定サイズを有する某数量％の粒子と言うような、数量％の粒子に関する記載がある場合、該粒子は同一容量％の該サイズの粒子を有することが好ましい。さらに、容量％の粒子に関する記載がある場合、該粒子は同一重量％の粒子を有することが好ましい。
実施例により、医薬錠剤芯の塗装方法および医薬錠剤芯の塗装用に適する数種の粉末塗装材料について、添付図面を参照しながら説明する。
図面において、図１は、錠剤芯塗装用装置の側面図を概略示し、図２は、図１の装置のドラムの断面を概略示す。
図１に概略図示した装置は、医薬錠剤芯の両面を塗装する装置である。本装置は、第１回転ドラム１２につながる、錠剤芯供給用傾斜シュートを含んでいる。ドラム１２は、スチール製であり且つその外表面に円形の窪み１４（図２）を有する。後で説明するように、吸引により各窪み内に錠剤芯が保持される。
ドラム１２は、矢印の方向に回転できる。ドラム１２の円周に近接し、錠剤供給シュート１０の下流に、静電噴霧ガン１６を含む準備位置Ａがあり、この位置は、錠剤芯の露出面をガン１６から発せられる荷電液滴で被覆する。準備位置の下流は、振動粉末皿１８を含む塗装位置Ｂであり、芯塗装用粉末を保持、流動化し且つ塗装領域Ｄ内での再循環を行う。塗装位置の下流はヒーター２０を含む溶融位置Ｃである。溶融位置Ｃを通過後、塗装芯は冷却位置（図示しない）を通過し、ここで冷却空気が錠剤上または周囲に誘導されて溶融した塗装を冷却する。
第２ドラム１２’は、第１ドラム１２に近接しており、ドラムの締付け部は溶融位置Ｃの下流になる。第２ドラム１２’は、矢印の如く第１ドラム１２に対向して回転する。第２ドラム１２’は、ガン１６’を含む準備位置Ａ’、粉末皿１８’を含む塗装位置Ｂ’、ヒーター２０’を含む溶融位置Ｃ’と冷却位置（図示しない）を装備している。
錠剤芯収集シュート２２は、溶融位置Ｃ’の下流で、第２ドラム１２’から離すように下方に傾斜していて、塗装済の錠剤芯を取り出し次の処理および包装工程につなげる。
第１ドラム１２について、図２を参照して詳細に説明する。このドラムは、回転可能な外板２４を含み、該外板の外側表面に窪み１４がある。図２には、代表的な５個の窪みだけを示してある。実際には、外板２４の周囲の円周列に非常に多くの窪みが均等に位置しており、またドラムの幅を横切る何本もの円周列があり、そこには１枚の連続外板または並んで固定された数枚の外板が形成されていることが判る。ドラム上の窪み１４の形状と寸法は、錠剤芯がドラム上にあるときに、芯の全片面と側壁の深さの１／２が露出するように保証されている。円形錠剤芯の場合、錠剤芯直径に近い窪み直径が好適である。或る適用例では、窪みの深さを、芯の厚みの少なくとも５０％になるように、塗装材料粒子に対し露出して、芯の最初の１面の露出、およびその後に他の面の露出を実施して芯を完全に被覆する。
ドラム上の各窪み１４は、その他の窪みと電気的に絶縁されており、且つ内方向に放射状に延び、しかしドラムの中心の手前で終わる摘出アーム２６をそれぞれ備えている。摘出アーム２６は、外板２４の内表面に取り付けられ、外板２４と共に回転する。各々関連する摘出アーム２６と窪み１４は、共に移動電極を形成し、窪み中の芯を帯電させる。それぞれの窪み１４は、重力のような外力に対抗する芯保持手段、例えば、吸引連結管３０に繋がっている壁を通る通路２８を有し、前記吸引連結管３０は外板と共に回転せず、ドラム周辺の一部の周囲に、第１ドラム１２と第２ドラム１２’間の締付け部に近接する芯供給シュートの直ぐ上流から内部に伸びている。
接地された固定のアーチ型第１電極３２は、準備位置Ａに相当する角度位置でドラム内側に置かれる。アースに対して電位差をもつ固定アーチ型第２電極３４は、塗装位置Ｂに相当する角度位置でドラム内側に置かれている。固定電局のアーチ外表面は、ドラムの中心から同一半径距離にあり、移動電極の摘出アーム２６の自由端になる。外板２４の回転に伴い、移動電極は第１、第２固定電極に順次接触する。ドラム１２は、塗装粉末のようにアースに対し同一電位差、好ましくは接地電位、好ましくは粉末皿１８に接続して保持される。
第２ドラム１２’は、第１ドラムと同様に構成され、窪みを備えた回転する外板、摘出アーム、と第１、第２固定電極、と吸引連結管から構成される。第１と第２固定電極の角度位置選定は、第２準備位置Ａ’と第２塗装位置Ｂ’に相当し、そして吸引連結管は、芯収集シュート２２に近接する２個のドラム間の締付け部の直ぐ上流から伸びている。
使用時、芯は連続的に芯供給シュート１０に供給される。芯は、芯供給シュート１０を下り、第１ドラム１２の回転外板２４中の窪み１４に入る。この角度位置で、窪みは吸引連結管３０上に位置し、それ故、前記芯は、外板中の通路２８による吸引で窪み中に保持される。外板２４は回転し続けて前記芯を準備位置Ａに運び、その地点で、窪み１４に取り付けた摘出アーム２６は、第１固定電極３２に接触して移動電極を接地し、このようにして芯が窪みに保持される。接地された錠剤芯が静電噴霧ガン１６を通過するときに、その露出表面に捕捉力向上液体、例えば、ポリエチレングリコールの帯電液滴が噴霧される。
外板２４は回転し続けて、錠剤が塗装位置Ｂに接近したとき、移動電極２６を第１固定電極３２との接触から外して第２固定電極３４と接触させる。ポリエチレングリコール処理した露出した芯表面は、アースに対して電位差を有し、塗装粉末材料は、静電気力により粉末皿１８から芯表面に誘導される。ドラム表面と粉末を互いにアースに対して同一電位差に且つ芯をアースに対して異なる電位差に保持することにより発生する電位は、粉末が芯に引きつけられるがドラム表面には実質的に粉末が付かない状態を保証している。
外板２４は回転し続けて、移動電極２６を第２固定電極３４との接触から外して、芯を溶融位置Ｃに運び、その位置でヒーター２０が芯の塗装表面の粉末を溶融して薄膜を形成させる。
外板２４が回転を続けるに伴い、芯は溶融位置Ｃを離れ、冷却位置（図示しない）を通過すれば、芯を運ぶ窪みは最早や吸引連結管３０上に位置しなくなる。芯は第１ドラム１２から第２ドラム１２’上の外表面にある窪み中に落下し、ドラム１２’上ではその非塗装表面を外向きにする。窪みは第２ドラムの吸引連結管３０に接続する。芯が第２準備位置Ａ’、塗装位置Ｂ’、溶融位置Ｃ’と冷却位置を移動するに従い、芯の塗装が完了する。第２塗装位置にある塗装粉末材料は第１塗装位置の塗装粉末材料と同一でもよく、また異なることもある。このようにすれば、異なって塗装された表面をもつ錠剤が製造できる。塗装した錠剤が収集シュートに近づくとき、芯を運ぶ窪みは吸引連結管から外れ、塗装錠剤はシュート中に落下し、そして更に処理、包装が行われる。
ドラム自体は、好適には、直径で少なくとも６０ｍｍであり、幅で最小錠剤直径より小でなく、少なくとも１／２ｒｐｍで回転する。吸引連結管の吸引圧力は、重力に対し錠剤を保持するに有効な大きさであり、好適には大気圧下で０．２〜０．６バールである。
準備位置Ａ、Ａ’における静電噴霧ガン１６と１６’で、半導電性の非蒸発性流体、例えばポリエチレングリコールまたはその水溶液が、０．１〜１ｍｌ／分の速度で内径０．０５〜２ｍｍのスチール製毛細管に供給される。ドラム上の各芯がガンを通過するとき、前記毛細管がアースに対し電位差をもつ電流制限した高電圧（３０〜１００μＡで最高５０ｋＶまで）に接続され、そして毛細管からドラム上の芯に向けて、帯電液滴の噴霧体が放射される。ドラム上の芯が準備位置で接地される故、帯電液滴が毛細管と芯間の電界により誘導され、芯の露出表面に達し、其処で捕捉される。芯は、準備位置において、対アース電位差で保持されるが、ただし芯が毛細管に対しても電位差を有する場合に限る。この場合、固定のアーチ型電極３２は、アースに対し電位差がある。各芯が準備位置を離れるとき、電圧を切ること及び抵抗（１〜１０ＭΩ）を介し毛細管を接地することにより、各毛細管からの液滴の供給が管理される。この方法は錠剤芯間の液滴の遮断をシャープにする。
塗装位置ＢとＢ’で、振動供給器により、粉末塗装材料が振動皿１８と１８’に供給される。各皿上で、ならし板を用いて皿中の粉末の高さを一定にする。粉末は振動流動化され、連続的に再循環される。前記の皿は、各ドラム上の錠剤芯により掃引されるアーク下で、アースされた金属小片を有するプラスティック材料製でもよく、または金属製でもよい。粒子帯電の新しい方法は、摩擦帯電的な帯電である。前記の皿は、好ましくは５０〜１５０ｍｍの長さと３〜４０ｍｍの幅である。２色または多色の面または１以上のポリマー組成物を有する面を提供するために、１以上の皿を使用するなら、皿の寸法はそれに相応しく変更できる。錠剤芯は、５μＡまでの制限電流で３〜１５ｋＶの電圧で帯電される。
溶融または乾燥位置ＣとＣ’で、芯表面にエネルギーを付与して粉末を溶融し、芯の露出表面に均一塗装を提供する。好ましくは、エネルギーの提供は赤外線領域の集束照射でなされる。エネルギーの性能要件は塗装材料で略決まる。溶融または乾燥後に、送風機を用いた冷却工程で、塗装は固定される。
本発明による好適な塗装装置は、毎時３００，０００錠剤芯まで塗装可能である。
図１と２を参照して上に記載した錠剤芯の塗装方法で、使用に適する粉末塗装材料の実施例を以下に説明する。
実施例１
乾燥粉末塗装材料を以下の方法で調整した。
（ａ）以下の化合物（重量％）を含有する試料を、高剪断ミキサーを用い前もって混合した。
５５．５％ ユードライトＲＳ（商標）（アンモニオ−メタクリレートコポリマー微粉体）
１８．５％ ポリエチレングリコール（高分子量：約２００００）
１５．０％ 二酸化チタン
５．０％ アルミニウムレーキ
５．０％ ラウリル硫酸ナトリウム
０．５％ エクスプロタブ（商標）（澱粉グリコール酸ナトリウム塩）
０．５％ アエロジル２００（商標）（コロイド性二酸化珪素）
混合前、前記試料の各成分の粒子サイズは下記の通りであった。
二酸化チタン ５０容量％が５μｍ以下
アルミニウムレーキ ５０容量％が１μｍ以下
ラウリル硫酸ナトリウム ５０容量％が１００μｍ以下
ユードライト ５０容量％が４０μｍ以下
ポリエチレングリコール ５０容量％が６０〜７０μｍ
（ｂ）前記の事前の混合物を下記の方法で湿式造粒した。上の（ａ）で得た混合物に水を徐々に添加し、高剪断ミキサー中で数分間混合して、粒状の混合物を得た。添加水の重量は、事前の混合物重量の約１０〜１５％であった。
（ｃ）上の（ｂ）工程で得た粒状の混合物を、流動床乾燥機中で約４５℃の温度で約２０〜３０分間乾燥して、３重量％以下の水分含有量（乾燥損失として測定）を有する材料を得た。
（ｄ）工程（ｃ）で得た小粒を衝撃粉砕した後、流動エネルギー粉砕機を用いて微粉砕して粉末を得た。該粉末は、５０容量％の粒子が２０μｍ以下のサイズで、殆ど１００容量％が６０μｍ以下のサイズであった。粒子サイズ分布のピークは約１０μｍのところに見られた。
粉末は、先に明示した静電気力の作用下で移動に敏感であった。
（ｅ）前記粉末で、前に記載した方法と装置を用いて、錠剤芯を塗装した。捕捉力向上液体による前処理は実施しなかった。赤外線源を用い錠剤芯上の塗装粉末を約１３０℃の温度に約５秒間加熱して、錠剤芯表面の粉末塗装を溶融させた。得られた塗装は、良好な不透明性を有し、滑らかで、光沢があり、そして明るい着色をしていた。塗装の厚みは１００μｍ以下であった。
上記工程（ｄ）で作成した粉末粒子の粒子サイズ分布を測定した。
１００％ ５７．２５μｍ以下
７０．２９％ ２２．０４μｍ以下
５．５８％ １．５２ μｍ以下
粒子の約５０％は、１５．０５μｍ〜３２．２９μｍサイズであった。
粒子の約３５％は、１８．２１μｍ〜３２．２９μｍサイズであった。
平均粒子サイズは、１９．１７μｍ（１つの方式で計算した）であった。
実施例２
以下の化合物（重量％）を含有する試料を用い、
５９．６％ ユードライトＲＳ（アンモニオ−メタクリレートコポリマー）
１９．９％ クルーセル（商標）（ヒドロキシプロピルセルソース）
１５．０％ 二酸化チタン
５．０％ アルミニウムレーキ
０．５％ クロスカルメロースナトリウム（架橋カルボキシメチルセルロースナトリウム）
実施例１の工程（ａ）から（ｄ）に記載の方法で、粉末塗装材料を作成した。実施例１の工程（ｅ）に記載したように、粉末材料を錠剤芯表面に塗装し、溶融させた。得られた塗装は、滑らかで、高光沢があり、強い色と良好な不透明性を有していた。この塗装は、従来の薄膜−塗装錠剤芯に期待する光沢に比べ、より高光沢であると判定した。
実施例３
以下の化合物（重量％）を含有する試料を用い、
３９．７５％ ユードライトＲＳ（アンモニオメタクリレートコポリマー）
３９．７５％ クルーセル（ヒドロキシプロピルセルソース）
１５．０％ 二酸化チタン
５．０％ アルミニウムレーキ
０．５％ アエロジル２００（コロイド性二酸化珪素）
実施例１の工程（ａ）から（ｄ）に記載の方法で、粉末塗装材料を作成した。実施例１の工程（ｅ）に記載したように、粉末材料を錠剤芯表面に塗装し、溶融させた。得られた塗装は、滑らかで、光沢があり、強い色と良好な不透明性を有していた。
実施例４
以下の化合物（重量％）を含有する試料を用い、
６０．０％ ユードライトＲＳ（アンモニオメタクリレートコポリマー）
２０．０％ グリセロールモノステアレート
１５．０％ 二酸化チタン
５．０％ アルミニウムレーキ
実施例１の工程（ａ）から（ｄ）に記載の方法で、粉末塗装材料を作成した。実施例１の工程（ｅ）に記載したように、粉末材料を錠剤芯表面に塗装し、溶融させた。得られた塗装は、滑らかで、無光沢であり、強い色と良好な不透明性を有していた。
実施例５
以下の化合物（重量％）を含有する試料を用い、
６０．０％ ユードライトＲＳ（アンモニオメタクリレートコポリマー）
２０．０％ キシリトール
１５．０％ 二酸化チタン
５．０％ アルミニウムレーキ
実施例１の工程（ａ）から（ｄ）に記載の方法で、粉末塗装材料を作成した。実施例１の工程（ｅ）に記載したように、粉末材料を錠剤芯表面に塗装し、溶融させた。得られた塗装は、半光沢で、強い色と良好な不透明性を有していた。
実施例６
以下の化合物（重量％）を含有する試料を用い、
４６．５％ ユードライトＲＳ（アンモニオメタクリレートコポリマー）
２８．０％ クルーセル（ヒドロキシプロピルセルソース）
１５．０％ 二酸化チタン
５．０％ アルミニウムレーキ
５．０％ ポリエチレングリコール６０００
０．５％ アエロジル２００（コロイド性二酸化珪素）
実施例１の工程（ａ）から（ｄ）に記載の方法で、粉末塗装材料を作成した。実施例１の工程（ｅ）に記載したように、粉末材料を錠剤芯表面に塗装し、溶融させた。得られた塗装は、滑らかで、強い色と良好な不透明性を有していた。
実施例７
以下の化合物（重量％）を含有する試料を、
５６．２５％ ポリエチレングリコール
２０．０％ 二酸化チタン
１８．７５％ ユードライトＲＳ（アンモニオメタクリレートコポリマー）
５．０％ アルミニウムレーキ
高剪断ミキサーを用いて調合した。調合前の状態では、ポリエチレングリコールとユードライトは、少なくとも５０容量％の１００〜２００μｍのサイズを有する粒子であって同様な粒子サイズであり、少なくとも５０容量％の二酸化チタンとアルミニウムレーキは、１μｍ以下のサイズを有していた。
（ｂ）乾燥した調合混合物を粉砕して、少なくとも５０容量％の粒子が１００〜２００μｍのサイズを有する３００μｍ以下の粒子サイズの粉末材料を得た。
（ｃ）ポリエチレングリコールの前処理噴霧を含む、上記の方法と装置を用いて、前記材料を錠剤芯に塗装した。赤外線源を用い錠剤芯上の塗装粉末を約１３０℃の温度に約５秒間加熱して、錠剤芯表面の粉末塗装を溶融させた。得られた塗装は、滑らかで、高光沢であり、強い色と良好な不透明性を有していた。この塗装は、従来の薄膜−塗装錠剤芯に期待する光沢に比べ、より高光沢であると判定した。
実施例８
以下の化合物（重量％）を含有する試料を、
５６．２５％ ポリエチレングリコール
２０．０％ 二酸化チタン
１８．７５％ ユードライトＲＳ（アンモニオメタクリレートコポリマー）
５．０％ アルミニウムレーキ
高剪断ミキサーを用いて乾燥調合し、調合混合物を実施例７の工程（ｂ）の記載のように粉砕した。なお、上記成分は、調合前には、実施例７に記載の粒子サイズと同様の粒子サイズを有していた（ポリエチレングリコールはユードライトと同様の粒子サイズ）。得られた材料を、実施例７の工程（ｃ）に記載したように、錠剤芯に塗装した。得られた塗装は、滑らかで、高光沢であり、強い色と良好な不透明性を有していた。この塗装は、従来の薄膜−塗装錠剤芯に期待する光沢に比べ、より高光沢であると判定した。
上記実施例では、全成分は粒子状の固体材料の形状であるが、粉末塗装材料は液体形状の成分を含有してもよい。The present invention relates to electrostatic coating of a pharmaceutical substrate with a powder coating material and powder coating material for coating a pharmaceutical substrate. In particular, the present invention relates to, but is not limited to, electrostatic coating of pharmaceutical tablet cores with powder coating materials and powder coating materials for pharmaceutical tablet core coatings. Reference is made to pharmaceutical tablets throughout the specification, and in particular, the present invention is often viewed as an application relating to conventional shaped pharmaceutical tablets, but this term refers to other products taken orally such as pellets, capsules and globules. Should be interpreted in a broad sense that also includes
Electrostatic coating of conductive substrates such as metal objects is well known. For example, in some paint spraying methods, the paint is charged and sprayed onto a metal object that is grounded. This method has been successful in forming a uniform coating film on a substrate.
Electrostatic coating of non-conductive substrates, especially pharmaceutical tablet cores, is quite difficult. For years, proposals have been made on electrostatic coating of tablets. For example, UK 1075404 proposes a device for tablet coating, in which fine particles of the coating solution are sprayed onto the tablets using a sprayer in a high potential field. As an example, the coating is dried using an infrared heater. However, this proposal has never been practiced on a substantially industrial scale, and the coating of pharmaceutical tablet cores is usually carried out batchwise by applying a liquid paint in a rotating drum. This liquid coating material may be supplied in powder form in some cases, but even if so, the coating material is used after being dissolved or dispersed in the liquid. Therefore, the coating material is not applied to the tablet core in powder form.
Application of liquid coating to pharmaceutical tablet cores is often easier than powder coating. It is difficult to fix the powder to the tablet, and in order to fix the coating to the core, it is necessary to convert the powder into a thin film without damaging the tablet core, which usually contains organic materials. Furthermore, uniform coating is required, and it is difficult to obtain a uniform powder coating on the tablet core.
If liquid paint is used, the paint must be dried. Theoretically, drying can be carried out at room temperature in some environments, however, tablet heating is important in the industry in terms of the speed at which the process is carried out, and the solvent used for liquid coating is evaporated. This is expensive because of the large amount of energy required. Another disadvantage of liquid coating is that useful liquids, preferably materials that do not dissolve or disperse properly in water, cannot be used for the coating material.
WO92 / 14451 relates to electrostatic powder coating of pharmaceutical tablets. The pharmaceutical tablet core is transported on a grounded conveyor belt, and electrostatically charged powder is sprayed toward the core to adhere to the core surface. Explains and illustrates how to form a powder coating. Thereafter, the powder coating is melted to give a molten film coating fixed to the core.
The disadvantage of such a method is that most of the powder sprayed towards the core is not charged and does not deposit on the core. This leads to waste of spray droplets and powder material, and makes it difficult to achieve uniform coating.
In a first aspect, the present invention attempts to provide a powder coating material suitable for electrostatic powder coating of pharmaceutical tablet cores, and provides a method for electrostatic coating of pharmaceutical tablet cores by using special powder coating materials. Attempts to facilitate electrostatic coating.
The first aspect of the present invention is to provide a powder coating material for use in electrostatic powder coating of tablet cores, particularly for coating methods defined below, and having special properties that give suitability for use in this method. It is. Preferably, the special properties of the powder coating material are defined below, and since the advantages afforded by these properties are influenced by the coating method employed, this method is also defined.
According to a first aspect of the present invention, the present invention provides a powder coating material suitable for electrostatic powder coating of a pharmaceutical tablet core, the material being pharmaceutically acceptable, capable of thin film coating processing, and Comprising composite particles, said composite particles being composed of two or more components having different physical and / or chemical properties.
It is important that the powder coating material is a pharmaceutically acceptable material. This in itself imposes severe constraints on powder coating materials, at least most of the powder coating materials commercially available for electrostatic powder coating processing are physiologically unacceptable and pharmaceutical tablets Commercially available materials for the core coating material are generally not suitable for electrostatic powder coating because of other inappropriate material properties.
The powder coating material of the present invention includes at least two different components, each having different physical and / or chemical properties. The use of a material composed of one or more components compared to the use of a one-component material makes it much easier to provide a powder material having the desired properties described above and elsewhere in the specification. For powder materials containing two or more extraneous components, we have found that improved coating is achieved when the powder contains several component composite particles.
If the coating method used is, for example, as described in the examples below, one or more coating material particles will be present if one or more of the components does not have the electrical properties required for coating on the core. It is particularly important to contain these components. If the particles are not composite particles, these particles consisting of components that do not have the required electrical properties may simply stay in the powder source and not be coated on the tablet core.
As used herein, the term “composite particle” refers to a particle formed from two or more different components. The composite particles are not homogeneous, and the composite particles have two or more regions each composed of fine particles of different components. The composite particles may be in the form of individual separate composite particles or may be agglomerates or aggregates of individual particles of different components, where the agglomerates or aggregates exhibit the behavior of separate composite particles. .
Advantageously, at least 50% by weight of the powder particles are composite particles. Ideally, virtually all particles need only be composite particles, which is not possible, especially when the particle size of the composite particles is small. If the powder includes two or more components having different physical and / or chemical properties, the composite particles advantageously also include other components. Ideally, virtually all composite particles are composed of individually separated particles that contain each of the heterogeneous components. However, in practice, satisfactory coating is obtained when the individual component particles form composite particles as aggregates or agglomerates.
Preferably two or more components are processed simultaneously. This simultaneous treatment consists of granulation, spray coagulation, spray drying or simultaneous grinding. If this co-treatment results in a relatively large size, for example granules, it is advantageous in some cases to carry out a subsequent grinding step to reduce the particle size. You may implement a miniaturization process newly.
As is well known, mixing of powder components usually results in a uniform mixture of components. However, in special cases, composite particles can be obtained by a mixing method by carefully selecting the mixing conditions, such as the initial particle size of the components and the mixing means.
According to the first aspect of the present invention, the powder coating material is a material that can be coated on the surface of the tablet core and then processed to form a thin film coating fixed to the core. Thus, the coating method of the present invention includes a step of forming a thin film coating fixed on the tablet core surface by processing the powder after coating the tablet core surface with powder. The thin-film coating is advantageously continuous, in which case the coating is not divided into separate parts, but there are small gaps that are not visible to the naked eye, for example, between the coating particles fixed together during the processing process. Existing. Thus, the paint is sintered. For some applications, it is preferred that no gaps exist in the thin film coating and / or that it be substantially homogeneous.
The powder material initially deposited on the tablet core is often easily removed by simply weakly adhering to the substrate surface. Because the mechanical strength of the tablet core itself is often small, the treatment to form a thin film coating is particularly advantageous when coating a pharmaceutical tablet core, and a thin film coating is used to provide strength, and the coated tablet To withstand the next process such as packaging and unpacking. Thin film coating can give the tablet core special strength, but is often very weak when separated from the core surface. The tensile strength of thin film coating as a free thin film is, for example, 8MNm-2Or less, and TiO in the coating material2It was found that the tensile strength decreased with increasing amount of.
When the tensile strength of the free thin film is small, it is particularly important that the thin film has a cohesive coating on the core surface with excellent adhesion to the tablet core.
When the powder material is converted into a liquid phase in the thin film coating forming step, the viscosity of the powder material in the liquid phase is preferably 500 Pascals or less, more preferably 75 Pascals or less.
It is an advantage that the powder coating material can be processed at a temperature of 250 ° C. or less, more preferably 200 ° C. or less, for forming a thin film coating. Conveniently, the powder coating material can be melted at a temperature below 250 ° C., more preferably below 200 ° C. under atmospheric pressure. It is important to process the powder without damaging the tablet core to form a coating around the tablet core, and this is due to the fact that many tablet cores containing organic materials are heat sensitive, so It imposes demands on it. The powder coating material preferably has a melting point in the range of 50C to 180C, more preferably in the range of 60C to 100C. For materials exhibiting a glass transition, the powder coating material preferably has a softening point in the range of 30 ° C to 180 ° C.
The above requirements place additional constraints on powder coating materials. Many materials do not melt and are carbonized by heat. Other materials that are meltable, however, need to be exposed to a heat source for a long time for melting, thus significantly increasing the risk of damage to the core and the time to form a thin film on the core. Unacceptable for economic reasons.
The desired temperature at which the powder coating material can be processed will, of course, depend on the material from which the tablet core is made, and for some materials the processing step may include temperatures above 250 ° C. In such cases, the exposure time to such high temperatures is reduced.
Preferably, the powder treatment to form the thin film coating includes a heating step, preferably a heating step using infrared radiation, and electromagnetic radiation, electromagnetic conduction, or electromagnetic induction can be used in other forms. The processing of the powder material can be carried out with partial or total pressure reduction around the tablet core. The change in powder material during processing is a simple physical change from solid to liquid and from cooling to a continuous solid film. Recently, powder materials can include polymers that can be cured during processing, such as polymers that cure by gamma radiation, ultraviolet light, or radio frequency energy irradiation to form a crosslinked polymer film.
We have found that the particle size of the powder coating material has a particularly important influence on the behavior of the material in the electrostatic powder coating process. It is advantageous that the particle size of the material is small. It is preferred that at least 95% by volume and at least 90% by volume of the powder material particles have a particle size of 50 μm or less. The term “particle size” refers to the corresponding particle diameter of a particle and can be measured, for example, using laser light diffraction.
Where the relevant particles are composite particles comprising agglomerates or aggregates of particles, the particle size is the size of the composite particles, not the size of individual particles in the agglomerates or aggregates.
Such particle sizes are remarkably small as coating materials for pharmaceutical tablet cores, and in fact, such small particle sizes are recognized as having the drawback of making the materials difficult to manufacture and handle due to their cohesiveness. Has been. However, we have found that the coating of pharmaceutical tablet cores by electrostatic coating methods has particular advantages in adopting small particle sizes and that there are additional advantages by eliminating the drawbacks. For example, the high surface to mass ratio provided by small particles increases the electrostatic force on the particles compared to the inertial force.
Increasing the electrostatic force has the advantage of increasing the force on the particle, which causes the particle to move into contact with the tablet core, while decreasing the inertial force reduces the force required to accelerate the particle and moves backward with the core. Reduces the possibility of particles that bounce and reach the tablet core. We have found that it is particularly advantageous when particles of at least 90% by volume of the powder material have a particle size of 20 μm or less. Preferably, at least 95% by volume of the powder material particles have a particle size of 30 μm or less.
In particular, for selected powder materials, if the particles tend to bounce off the surface of the tablet core, hold the tablet core in close proximity to the powder material source after applying the pretreatment composition to the surface of the tablet core. Let The pretreatment composition was able to improve particle capture by the core surface and enabled the use of large particles as large as 750 μm as the coating material. A liquid can be used in the pretreatment composition to increase the force acting on the particles and keep the particles on the core. When pretreatment is employed, preferably at least 90% by volume of the particles are 300 μm or less in size, and preferably at least 50% by volume of the particles are 200 μm or less in size.
When the particle size becomes very small, the difficulty in handling the powder becomes severe. Thus, it is advantageous that at least 50%, preferably at least 75%, optimally 90% by volume of the powder has a particle size of at least 5 μm.
In one preferred powder coating material, the average particle diameter is about 10 μm and does not include particles having a diameter substantially greater than 100 μm.
Suitably, at least 30% by volume of the powder particles have a particle size in the range of 5 μm to 25 μm.
We have found that it is also particularly important that the powder particles have a narrow range of particle sizes. Preferably at least 30 wt%, more preferably at least 75 wt% of the particles are in the range x to 2x, more preferably in the range x to 1.5x, optimally in the range x to 1.25x. Has a particle size, where x represents the particle size of the powder.
For example, in a powder having relatively small size particles, preferably at least 30% by weight of the particles are in the range of 10 μm to 20 μm, more preferably in the range of 10 μm to 15 μm, optimally in the range of 10 μm to 12.5 μm. Have a particle size of
If the particles are relatively large, for example pretreatment as described above, the preferred relative variation in particle size is usually smaller than for relatively small size particles.
We have found that powders with a large particle size range are disadvantageous compared to powders with a small particle size range for performing a good uniform application of the powder on the tablet core and from core to core. It was. This is thought to be because particles having a certain particle size are preferentially painted on the tablet core when compared to smaller or larger sized particles. This means that there is a difference in the quality of the coating of the core and the change in the quality of the coating, with one painted core painted with a powder material of a newly tailored batch and another painted core coated relatively later in the same batch. It is connected.
Moisture content of powder coating material not more than 10% by weight, preferably not more than 5% by weight, more preferably not more than 3% by weight, based on the weight of the powder coating material (measured by moisture loss during drying) It is convenient to have
There are several different electrostatic effects, and in accordance with the first aspect of the present invention, can be used in electrostatic coating methods using powders to coat pharmaceutical tablet cores, and several different powders that are particularly adapted to the utilization of different effects. Has electrical characteristics. Three different effects and related properties of the powder are described here, and it must be appreciated that each can be used independently of the other or in connection with one or more of the other.
The first possibility is to induce a temporary dipole in the particles of the powder, after which the particles become tablet cores due to the interaction of the dipole with the electric field in the region between the powder source and the tablet core. Led in the direction of. Preferably the coating material is 108-1016Has a specific resistance in the range of Ωm.
A second possibility is to apply a net charge to the powder particles. This net charge is introduced triboelectrically or by corona charging. Therefore, the coating material is preferably receptive to such a net charge and can retain the charge (long enough to guide the material well onto the tablet core).
A third possibility is to give the powder particles a permanent or semi-permanent dipole. Such “electrets” will be directed in the direction of the tablet core by the interaction of the electric field acting on the area between the powder source and the tablet core. Thus, the coating material may include an electret.
A fourth possibility is to provide a magnetic dipole in the powder material using iron or other magnetic material or paramagnetic material.
It is preferred that the powder material can be directed to the tablet core without depending on the overall net charge applied to the powder material and without depending on the permanent implant charge in the powder material. Thus, it is preferred that the powder material be sensitive to movement under the action of electrostatic forces, which sensitivity is measured by the tests specified below.
To determine whether a powder material is sensitive to movement under the influence of electrostatic forces, the following test is performed.
A sample of 0.5 g of powder material is taken and placed on a conductive metal plate placed horizontally and kept at ground potential in an environment with a relative humidity not greater than 65%. This powder material is expanded to a thickness close to a monomolecular layer. After the powder material is left in that state for 30 minutes, a round metal probe with a diameter of 5 mm is placed 10 mm above the center of the powder material, the high voltage is first +10 KV, then -10 KV (current limited to about 5 μA) ) And apply to the probe for about 10 seconds. If the particles of the powder material that represent the material as a whole are attracted upward and contact the probe during either high voltage application, the test results show that the powder material moves under the action of electrostatic force. To be sensitive to. If the particles of the powder material are not attracted upwards and do not contact the probe, or if only certain particles are attracted and the attracted particles are not representative of the material as a whole, the test result is The powder material will not be sensitive to movement under the action of electrostatic forces.
The sensitivity of the powder material naturally depends on the combination of the electrical properties of the powder and other physical properties such as the particle size of the powder.
In order for the particles of the coating material to be charged (eg, triboelectrically) and adhere to the core surface, it is particularly advantageous for the particles to be substantially all of the same symbolic charge. It has been found that an unsatisfactory coating forms on the core surface when a group of particles contains a mixture of positive and negative charges. When the powder is charged, it is preferable that the powder is composed of a composition in which the whole powder has substantially the same symbol charge. Furthermore, if the particles are not of the same symbolic charge, the powder material is oversprayed, reducing the efficiency of the painting process. It is also preferred that most particles have substantially the same charge.
Since the material consists of more than one component, the properties of the powder material can be altered by adjusting the relative proportions of the components. In general, when referring to the properties of a powder material, that property is the property exhibited by the material as a whole, and that one or more components of the material do not exhibit that property alone. . However, it is satisfactory if one or several components of the powder coating material, rather than the powder coating material as a whole, exhibit the following properties: for example, forming a thin film coating at low temperatures The advantages of the material are achieved by only one of the two or more components of the material exhibiting its properties; other components remain solid particles and are larger than particles that convert to a thin film coating. In such a case, there is a substantial variation in the particle sizes of the two components; for example, particles converted to thin film coating have a particle size in the range of 5-20 μm, while solids The particles that remain as particles are substantially larger.
One of the extraneous components may serve to provide the necessary electrostatic properties to the powder material. For example, one extraneous component is triboelectrically and / or coronaally charged and / or becomes an electret or magnet and / or under the action of electrostatic forces as defined in the tests described herein. May be sensitive to movement.
The chemical properties of the powder material are important for the efficiency and appearance of forming the paint.
When discussing the chemical properties of a material, it is advantageous to process a material composed of multiple components, and as will be apparent from the discussion below, the same compound is used as one or more components, and therefore a powder. References in the following description relating to the material consisting of two or more components require that two or more dissimilar components are necessarily present, unless the components are specifically considered different. Should not be considered.
The powder material preferably contains a first component that can be melted at a temperature of 250 ° C. or lower, more preferably 200 ° C. or lower to form a continuous thin film on the core surface. As discussed above, melting can take the form of melting, softening or crosslinking of the first component within the above temperature range.
It is preferred that the first component is substantially soluble in the aqueous medium. Usually, the first component is soluble in a neutral aqueous medium and only dissolves in a selected PH range, such as PH3 to PH6, or PH8 to PH14.
Preferably, the first component consists of polyoxyethylene, sugar alcohol, and one or more of unsaturated or saturated fatty acids and esters. The first component can include a cellulose derivative that melts at a temperature of 250 ° C. or lower, such as hydroxypropylcellulose. Not all cellulose derivatives can be used as the first component, for example hydroxypropylmethylcellulose does not have the required melt properties and carbonizes upon heating.
The first component can include polyethylene glycol, which has good melt properties and can form a good continuous thin film on the substrate surface after processing.
A suitable sugar alcohol is xylitol, which material has suitable electrical properties and melts at a suitable temperature and is useful as a coating material in the coating of pharmaceutical tablet cores.
Other materials that can be used as the first component include waxes and oils, wax or oil alcohols, poloxamers, alkylnaphthalenes such as diethyl phthalate, citric acid and esters. When the powder component is a liquid, the component can simply be added to the other components in liquid form and may be provided with a carrier material, for example in powder form.
Other compounds with suitable melting properties may exist and the above is merely exemplary.
The first component may consist of exactly one compound or may contain two or more compounds.
In many cases, the component with the most desirable melt properties does not provide the optimal electrical properties and / or does not provide the desired finish, coating or appearance of the paint. Therefore, it is preferable to use the second component having the necessary electrical characteristics as described above.
However, it should be understood that the first component may have the desired electrical properties of the second component, and the second component may have the desired melting properties of the first component.
The second component includes acrylic acid, polymers and copolymers of acrylic acid and derivatives thereof such as polymethyl acrylate, polyalkene and derivatives thereof, esters, aryl esters and derivatives thereof, polyvinyl alcohol and esters, cellulose and derivatives thereof such as cellulose It consists of one or more ethers and cellulose esters (crosslinked or non-crosslinked), such as ethyl cellulose, one or more enteric polymers such as cellulose acetate phthalate and hydroxypropyl methylcellulose phthalate. The second component is one of one or more biodegradable polymers such as polylactide, polyglycolide, polyhydroxybutyrate, polyhydroxyvalerate, ethylene vinyl acetate copolymer, and polyanhydride (homo or heteropolymer). One or more may be included. The second component may be polyethylene oxide.
As already mentioned, the first component and the second component may contain the same compound, but in many cases the first and second components are different compounds. For example, the first and second components may each contain xylitol, but in this case a viscosity modifier and a crystallization inhibitor should be added to give the second component the desired melt characteristics.
Preferably, the coating material comprising two or more extraneous components includes a dispersant component that improves the dispersion of the extraneous components. The dispersant component is preferably an anionic, cationic or nonionic surfactant, but may be other compounds which are not usually called surfactants but have similar effects. The dispersant component may be a co-solvent.
The dispersant component may be, for example, one or more of sodium lauryl sulfate, docusate sodium, tween (sorbitan fatty acid ester), poloxamer, and cetostearyl alcohol. Like the first and / or second component compounds, the dispersant component may comprise the same compound. As described above, both the third and first components may include a poloxamer. It is preferred that the material comprises at least 1%, preferably 2-5% by weight of a dispersant component, based on the weight of the material.
It is advantageous for the powder coating material to contain an anti-friction component to reduce frictional forces and / or other forces between the powder coating material particles and improve the flowability of the powder. Anti-friction components include titanium dioxide, colloidal silica, talc or starch, or mixtures thereof.
When the coating material is used in “immediate” release tablets, it is advantageous that the powder coating material includes a disintegrant that can break the coating. In the case of a coating on the tablet core, the inclusion of a disintegrant during coating accelerates the disintegration of the coating immediately when the tablet is ingested.
Disintegrants are those that swell rapidly and strongly when contacted with moisture, thereby destroying the coating. Some disintegrants swell and become 40 times their original volume within seconds. Examples of suitable disintegrants are starch glycolic acid sodium salt (cross-linked) and carboxymethylcellulose sodium salt (cross-linked).
Alternatively or in addition, the disintegrant may be a wicking type, which allows moisture to penetrate through the coating into the tablet core, but prevents back-flow of moisture through the coating from the tablet core and thereby destroys the coating. Examples of suitable wicking type disintegrants are natural starch, cross-linked polyvinyl pyrrolidone (CrossProvidone).
The disintegrant may be a gas generating type such as sodium carbonate, sodium bicarbonate and sodium glycinate.
Preferably, the powder coating material contains up to 10% by volume of disintegrant. Preferably, the powder contains 5 wt% or less, preferably 2 wt% or less, more preferably 1 wt% or less, and optimally about 0.5 wt% disintegrant.
Preferably, the powder coating material further contains one or more opacifiers such as titanium dioxide and talc. Preferably, the material comprises 50 wt% or less, preferably 40 wt% or less, more preferably 30 wt% or less, and most preferably about 10 wt% or less of the opacifier based on the weight of the material.
Preferably, the powder coating material further comprises one or more colorants, such as metal oxides or lakes, such as aluminum lakes, iron oxides, dyes, and one or more taste modifiers, such as aspartame, acesulfame. k, cyclamate, saccharin, sugar, sugar alcohol or flavoring agents, and the like. Preferably, the material comprises 10% by weight or less, preferably 1-5% by weight, based on the weight of the material, and preferably 5% by weight or less, based on the weight of the material. More preferably, it contains 1% by weight or less of a flavoring agent. When the flavoring agent is a sweetener, preferably the material contains 0.5% by weight or less of the sweetener. Preferably, the material comprises 5% by weight or less of colorant and flavor based on the weight of the material. It will be appreciated that the anti-friction component, opacifier, colorant and taste modifier may be the same compound as the other component compounds of the powder coating material.
Powder coating materials can contain bioactive materials, which are materials that increase or decrease process speed in a biological environment. The bioactive material may be a physiologically active material. The coating material containing the active material can be applied, for example, to a tablet core containing the same or different active material, or to a non-active material containing tablet core. The active material can contain one or more compounds. Active materials include acid digestion and exercise inducers, laxatives, antidiarrheals, colon and rectal drugs, pancreatic enzymes and bile acids, antiarrhythmic drugs, antianginal drugs, diuretics, antihypertensive drugs, anticoagulants, anticoagulants Thrombotic drugs, fibrinolytic drugs, hemostatic drugs, fat deficiency drugs, anti-anemic / neutropenic drugs, hypnotics, anti-anxiety drugs, antipsychotic drugs, antidepressants, antiemetics, antispasmodics, CNS stimulants, analgesia Drugs, antipyretic drugs, anti-migraine drugs, non-steroidal anti-inflammatory drugs, anti-ventilants, muscle relaxants, neuromuscular drugs, steroids, hypoglycemia drugs, hyperglycemia drugs, diagnostic drugs, antibiotics, antifungal Drugs, antimalarial drugs, antiviral drugs, immunosuppressive drugs, nutritional drugs, vitamins, electrolytes, appetite suppressants, appetite suppressants, bronchodilators, expectorants, antitussives, mucolytic drugs, decongestants, antiglaucoma Including drugs, oral contraceptives, and / or anti-neoplastic agents.
Tablet cores to which the powder coating material is applied usually contain one or more inert chemicals. Inert chemicals include diluents such as lactose, sucrose, glucose, starch, cellulose, microcrystalline cellulose; binders such as polyvinylpyrrolidone, starch mucus, gelatin, gum arabic; disintegrants such as cross-linked carboxymethylcellulose sodium salt, Sodium starch glycolate, crosslinked polyvinylpyrrolidone; Lubricants such as magnesium stearate, sodium stearyl fumarate; glidants such as colloidal silica, talc; surfactants such as wetting agents, sodium lauryl sulfate, docusate sodium; coloring Agents; can include flavoring agents and / or gas generants such as sodium bicarbonate and citric acid.
The tablet core can also include one or more of the active materials listed above. Preferably, the powder coating material comprises at least 0.5% by weight of active material, more preferably 1% by weight, based on the weight of the powder coating material. For example, a 10 mg coating on a tablet can contain approximately at least 0.05 mg of active material.
The ratio of mixing the components of the powder coating material largely depends on the properties of the material constituting the powder coating material and the substrate to be coated. The ratio is adjusted to achieve the desired electrical and melting characteristics. Usually, the powder coating material contains at least 10%, preferably at least 15%, optimally about 20% by weight of the first component. Usually, the powder coating material contains at least 10% by weight, preferably at least 20% by weight, and more preferably at least 40% by weight of the second component, in each case based on the weight of the powder coating material. Preferably, the weight ratio of the second component to the first component is about 3: 1. The component ratio depends on the materials constituting the first and second components. The ratio is 2: 1 or 1: 1.
The present invention further provides a coating material for electrostatic coating of a pharmaceutical substrate, the coating material containing an active material. As indicated above, the coating material containing the active material is applied to a tablet core containing, for example, the same or different active material, or applied to a core containing an inactive material.
When trying to manage a very small dose of active material in tablet form, the active material is mixed with a large amount of non-active “fill” material to create a manageable size tablet. Traditionally, the active material and the filling material were simply mixed together and the intake of the resulting mixture was tableted. It has been found that accurate management of the amount of active material contained in each tablet is difficult, and the uniformity of intake is insufficient. This was especially observed when the amount of active material required by each tablet was small.
It has been found that by applying the active material to the tablet surface, a very small amount of active material can be accurately applied to the tablet and the reproducibility of the intake can be improved.
The amount of active material contained in the coating material will of course depend on the amount of active material intake applied to the substrate and the thickness of the coating formed. Usually, the material contains at least 0.5% by weight of active material, based on the weight of the coating.
Conveniently, the coating material is a powder coating material. It is therefore convenient to apply the coating material using a method similar to that described above, and the coating material is applied to the substrate accurately and without overspraying.
Preferably, the coating material containing the active material contains at least 90% by volume of particles having a particle size not greater than 50 μm. Preferably, at least 90% by volume of the powder particles have a particle size of 30 μm or less, more preferably 20 μm or less.
The present invention also provides the use of a coating material comprising an active material in electrostatic coating of a substrate, particularly in the electrostatic coating of a pharmaceutical tablet core.
The first aspect of the present invention also provides a method of electrostatically coating a pharmaceutical tablet core with a powder material, and a powder material as defined above.
Furthermore, the 1st viewpoint of this invention provides the powder coating material for electrostatic coating of a base material, and a powder is obtained by the above methods.
Still further, a first aspect of the present invention provides a pharmaceutical tablet comprising a tablet core and a powder coating material as defined above.
Furthermore, a first aspect of the present invention provides a method of coating a pharmaceutical tablet core with powder, the method holding the tablet core in proximity to a source of powder coating material in an electric field, and at least the core. This portion is held at a potential different from the potential of the coating material, and a potential difference is applied to guide the powder from the powder source in the direction of the tablet core and the core surface, and the powder coating material is applied.
Since the coating of the tablet core induces the powder material towards the tablet core as a result of the application of an electric field and at least the potential difference between the tablet core portion and the powder material, the point of arrival of the powder material is at least initially the tablet. Limited to the surface of the wick. If it is arranged only on the exposed surface, it is in the vicinity of the powder material and where there is an appropriate potential difference with respect to the powder material.
A special advancement of the method is that it can be carried out in a continuous process.
It is advantageous to transfer the tablet core by transfer means through an area proximate to the source of powder coating material. By transferring the tablet core, it can be ensured that the tablet core is handled gently throughout the coating process and that even the fragile tablet core is not damaged.
This method can be used to coat tablet cores that are fragile and cannot withstand conventional tablet coating methods. Thus, the present invention has made it possible to produce tablets having a conventional shape and having a wide range of compositions. Also, unconventional shaped tablets, for example, tablets that are not conventional circular surfaces but rather have opposite planes can be produced by the method of the present invention. Such flat tablets are usually very fragile and could not be painted by conventional methods. Furthermore, plane tablets are often joined together to form twin tablets and groups of tablets, which could not be properly painted by conventional coating methods.
The tablet core is held from the top close to the powder coating material source and the powder moves from above the source to the lower surface of the substrate.
The tablet core produced by the coating method specified above is simply a partial coating, and this coating method includes the following further steps, which are applied in the vicinity of the powder coating material source in an electric field. Holding the tablet core, maintaining at least a portion of the tablet core at a potential different from the potential of the coating material, applying a potential difference to direct the powder from the powder source toward the tablet core, and uncovering the uncoated surface of the tablet core It is to be painted with powder coating material. In this way, it is possible to easily apply to the entire surface of the tablet core, and it is also possible to apply different parts of the tablet core with different coating materials. For example, different colors can be applied to each opposite side of the tablet.
Furthermore, the 1st viewpoint of this invention provides the pharmaceutical tablet which gave electrostatic coating by the method specified above.
In accordance with the first aspect of the present invention, powder coating materials and coating methods have been developed, especially for pharmaceutical tablet core coatings and to address the harsh conditions that can be imposed on the material from the application of the coating. Although materials and methods have been developed that are suitable for pharmaceutical tablet core coatings, we have further expanded our thinking to other uses where the materials and methods can be used effectively. For example, in the pharmaceutical industry, the materials and methods can be used to paint other pharmaceutical products that are not taken orally, for example, pessaries, boogies or suppositories, or other pharmaceutical substrates.
According to a second aspect of the present invention, there is provided a powder coating material for electrostatic powder coating of a pharmaceutical substrate, the material having one or more of the following properties.
a) suitable for human and / or animal consumption;
b) consisting of at least two foreign components, preferably the particles consist of composite particles,
c) A thin film coating is formed by melting at a temperature of 250 ° C. or less at atmospheric pressure.
d) at least 30% by weight of the particles have a particle size ranging from 5 μm to 20 μm,
e) It is sensitive to movement under the action of electrostatic force, and its sensitivity is measured by the test method specified here.
It is particularly preferred that the powder coating material is a physiologically acceptable material and preferably a pharmaceutically acceptable material. The material can have other properties as described above in the description of the pharmaceutical tablet core coating material.
The present invention also provides a method for producing a powder coating material comprising at least two extraneous components for electrostatic coating of a substrate, the method comprising the step of simultaneously treating the at least two extraneous components. It is a waste.
Furthermore, the second aspect of the present invention provides a method of electrostatically coating a pharmaceutical substrate with the powder coating material specified above.
Here, when there is a description relating to a number% of particles having a specific size, such as a number% of particles, it is preferable that the particles have the same volume% of the particles of the size. Furthermore, when there is a description about the volume% particles, it is preferred that the particles have the same weight% particles.
By way of example, a method for coating a pharmaceutical tablet core and several powder coating materials suitable for coating a pharmaceutical tablet core will be described with reference to the accompanying drawings.
In the drawings, FIG. 1 schematically shows a side view of an apparatus for coating a tablet core, and FIG. 2 schematically shows a cross section of a drum of the apparatus of FIG.
The apparatus schematically illustrated in FIG. 1 is an apparatus for coating both sides of a pharmaceutical tablet core. The apparatus includes an inclined chute for supplying a tablet core that is connected to the first rotating drum 12. The drum 12 is made of steel and has a circular depression 14 (FIG. 2) on its outer surface. As will be described later, the tablet core is held in each recess by suction.
The drum 12 can rotate in the direction of the arrow. Near the circumference of the drum 12 and downstream of the tablet supply chute 10, there is a preparation position A containing an electrostatic spray gun 16, which covers the exposed surface of the tablet core with charged droplets emitted from the gun 16. To do. Downstream of the preparation position is the coating position B including the vibrating powder dish 18, which holds and fluidizes the core coating powder and recirculates in the coating area D. Downstream of the painting position is a melting position C including the heater 20. After passing through the melting position C, the coating core passes through a cooling position (not shown) where cooling air is induced on or around the tablet to cool the molten coating.
The second drum 12 ′ is close to the first drum 12, and the drum tightening portion is downstream of the melting position C. The second drum 12 'rotates opposite the first drum 12 as indicated by an arrow. The second drum 12 'is equipped with a preparation position A' including a gun 16 ', a coating position B' including a powder pan 18 ', a melting position C' including a heater 20 ', and a cooling position (not shown).
The tablet core collecting chute 22 is inclined downwardly away from the second drum 12 'downstream of the melting position C', and the coated tablet core is taken out and connected to the next processing and packaging process.
The first drum 12 will be described in detail with reference to FIG. The drum includes a rotatable skin 24 with a recess 14 on the outer surface of the skin. In FIG. 2, only five representative depressions are shown. In practice, a large number of depressions are evenly positioned in the circumferential row around the outer plate 24, and there are a number of circumferential rows across the width of the drum, where there is one continuous outside It can be seen that a plate or several outer plates fixed side by side are formed. The shape and dimensions of the indentations 14 on the drum are guaranteed such that when the tablet core is on the drum, one half of the core core and half the side wall depth are exposed. In the case of a round tablet core, a recess diameter close to the tablet core diameter is preferred. In some applications, the depth of the depression is exposed to the coating material particles so that it is at least 50% of the thickness of the core, exposing the first surface of the core, and then exposing the other surface. To completely cover the core.
Each indentation 14 on the drum is provided with an extraction arm 26 that is electrically isolated from the other indentations and extends radially inward, but ends in front of the center of the drum. The extraction arm 26 is attached to the inner surface of the outer plate 24 and rotates together with the outer plate 24. Each associated extraction arm 26 and depression 14 together form a moving electrode and charge the core in the depression. Each recess 14 has a core holding means that opposes an external force such as gravity, for example, a passage 28 passing through a wall connected to the suction connection pipe 30, and the suction connection pipe 30 does not rotate with the outer plate, Around a part of the periphery of the drum, it extends inward from immediately upstream of the lead supply chute close to the tightening portion between the first drum 12 and the second drum 12 ′.
The grounded fixed arched first electrode 32 is placed inside the drum at an angular position corresponding to the preparation position A. The fixed arched second electrode 34 having a potential difference with respect to the ground is placed inside the drum at an angular position corresponding to the painting position B. The arch outer surface of the fixed station is at the same radial distance from the center of the drum and becomes the free end of the extraction arm 26 of the moving electrode. As the outer plate 24 rotates, the moving electrode sequentially contacts the first and second fixed electrodes. The drum 12 is held by being connected to the same potential difference with respect to the ground as in the case of coating powder, preferably the ground potential, preferably the powder dish 18.
The second drum 12 ′ is configured in the same manner as the first drum, and includes a rotating outer plate having a recess, an extraction arm, first and second fixed electrodes, and a suction connection tube. The selection of the angular positions of the first and second fixed electrodes corresponds to the second preparation position A ′ and the second painting position B ′, and the suction connection pipe is tightened between the two drums close to the core collecting chute 22. It extends from just upstream of the department.
In use, the lead is continuously supplied to the lead supply chute 10. The lead descends the lead supply chute 10 and enters the recess 14 in the rotating outer plate 24 of the first drum 12. In this angular position, the recess is located on the suction connection tube 30, so that the core is held in the recess by suction by the passage 28 in the skin. The outer plate 24 continues to rotate and carries the core to the preparation position A, at which point the extraction arm 26 attached to the recess 14 contacts the first fixed electrode 32 and grounds the moving electrode, thus The core is held in the recess. As the grounded tablet core passes through the electrostatic spray gun 16, a capture-enhancing liquid such as a charged droplet of polyethylene glycol is sprayed onto its exposed surface.
The outer plate 24 continues to rotate, and when the tablet approaches the coating position B, the moving electrode 26 is removed from contact with the first fixed electrode 32 and brought into contact with the second fixed electrode 34. The exposed core surface treated with polyethylene glycol has a potential difference with respect to the ground, and the coating powder material is guided from the powder dish 18 to the core surface by electrostatic force. The potential generated by holding the drum surface and the powder at the same potential difference with respect to ground and the core at a different potential difference with respect to the ground causes the powder to be attracted to the core, but the drum surface is substantially free of powder. The state is guaranteed.
The outer plate 24 continues to rotate, removes the moving electrode 26 from contact with the second fixed electrode 34, carries the core to the melting position C, where the heater 20 melts the powder on the coating surface of the core, and forms a thin film. To form.
As the outer plate 24 continues to rotate, if the core leaves the melting position C and passes through the cooling position (not shown), the recess for carrying the core is no longer positioned on the suction connection pipe 30. The wick falls from the first drum 12 into a recess in the outer surface on the second drum 12 ', with its unpainted surface facing outward on the drum 12'. The depression is connected to the suction connecting pipe 30 of the second drum. As the lead moves between the second preparation position A ', the coating position B', the melting position C 'and the cooling position, the coating of the lead is completed. The coating powder material at the second painting position may be the same as or different from the coating powder material at the first painting position. In this way, tablets with differently painted surfaces can be produced. As the coated tablet approaches the collection chute, the dent carrying the wick disengages from the suction connection tube, the coated tablet falls into the chute and is further processed and packaged.
The drum itself is preferably at least 60 mm in diameter and not less than the minimum tablet diameter in width and rotates at least 1/2 rpm. The suction pressure of the suction connecting pipe is of a size effective for holding the tablet against gravity, and is preferably 0.2 to 0.6 bar under atmospheric pressure.
In the electrostatic spray guns 16 and 16 ′ at the preparation positions A and A ′, a semiconductive non-evaporable fluid, such as polyethylene glycol or an aqueous solution thereof, has an inner diameter of 0.05 to 2 mm at a speed of 0.1 to 1 ml / min. Supplied to steel capillaries. As each core on the drum passes through the gun, the capillary is connected to a current limited high voltage with a potential difference to ground (up to 50 kV at 30-100 μA), and from the capillary to the core on the drum, A spray of charged droplets is emitted. Since the core on the drum is grounded at the ready position, charged droplets are induced by the electric field between the capillary and the core, reach the exposed surface of the core and are captured there. The core is held at the preparation position with a potential difference with respect to ground, but only if the core has a potential difference with respect to the capillary. In this case, the fixed arched electrode 32 has a potential difference with respect to the ground. As each core leaves the preparation position, the supply of droplets from each capillary is controlled by turning off the voltage and grounding the capillary through a resistor (1-10 MΩ). This method sharpens the blockage of the droplets between the tablet cores.
At the coating positions B and B ', the powder coating material is supplied to the vibration dishes 18 and 18' by the vibration feeder. On each dish, a leveling plate is used to keep the powder height constant in the dish. The powder is vibrated and continuously recirculated. Said dish may be made of plastic material with metal pieces grounded under an arc swept by a tablet core on each drum, or may be made of metal. A new method of particle charging is triboelectric charging. The dish is preferably 50 to 150 mm long and 3 to 40 mm wide. If more than one dish is used to provide a two-color or multicolored surface or a surface having one or more polymer compositions, the dimensions of the dish can be changed accordingly. The tablet core is charged with a voltage of 3-15 kV with a limiting current up to 5 μA.
In melting or drying positions C and C ', energy is applied to the core surface to melt the powder and provide a uniform coating on the exposed surface of the core. Preferably, the energy is provided by focused irradiation in the infrared region. Energy performance requirements are largely determined by the coating material. After melting or drying, the coating is fixed in a cooling process using a blower.
A preferred coating device according to the present invention is capable of painting up to 300,000 tablet cores per hour.
Examples of powder coating materials suitable for use in the tablet core coating method described above with reference to FIGS. 1 and 2 are described below.
Example 1
The dry powder coating material was prepared by the following method.
(A) Samples containing the following compounds (wt%) were pre-mixed using a high shear mixer.
55.5% Udolite RS ™ (ammonio-methacrylate copolymer fine powder)
18.5% polyethylene glycol (high molecular weight: about 20000)
15.0% titanium dioxide
5.0% aluminum rake
5.0% sodium lauryl sulfate
0.5% Exprotab ™ (starch glycolate sodium salt)
0.5% Aerosil 200 ™ (colloidal silicon dioxide)
Prior to mixing, the particle size of each component of the sample was as follows.
Titanium dioxide 50% by volume is 5μm or less
Aluminum lake 50% by volume is less than 1μm
Sodium lauryl sulfate 50% by volume is 100μm or less
Eudolite 50% by volume is 40μm or less
Polyethylene glycol 50% by volume is 60 to 70 μm
(B) The previous mixture was wet granulated by the following method. Water was gradually added to the mixture obtained in (a) above and mixed for several minutes in a high shear mixer to obtain a granular mixture. The weight of the added water was about 10-15% of the premix weight.
(C) The granular mixture obtained in step (b) above is dried in a fluid bed dryer at a temperature of about 45 ° C. for about 20-30 minutes to a moisture content of 3% by weight or less (as drying loss) A material having (measurement) was obtained.
(D) The small particles obtained in step (c) were impact pulverized and then finely pulverized using a fluid energy pulverizer to obtain a powder. The powder had a size of 50% by volume of particles of 20 μm or less and almost 100% by volume of 60 μm or less. The peak of the particle size distribution was observed at about 10 μm.
The powder was sensitive to movement under the action of the electrostatic force specified above.
(E) A tablet core was coated with the powder using the method and apparatus described previously. No pretreatment with the trapping power enhancing liquid was performed. The coating powder on the tablet core was heated to a temperature of about 130 ° C. for about 5 seconds using an infrared source to melt the powder coating on the tablet core surface. The resulting coating had good opacity, was smooth, glossy and brightly colored. The coating thickness was 100 μm or less.
The particle size distribution of the powder particles prepared in the step (d) was measured.
100% 57.25 μm or less
70.29% 22.04 μm or less
5.58% 1.52 μm or less
About 50% of the particles were 15.05 μm to 32.29 μm in size.
About 35% of the particles were 18.21 μm to 32.29 μm size.
The average particle size was 19.17 μm (calculated in one way).
Example 2
Using a sample containing the following compound (% by weight)
59.6% Eudolite RS (ammonio-methacrylate copolymer)
19.9% Crucell ™ (hydroxypropyl cell sauce)
15.0% titanium dioxide
5.0% aluminum rake
0.5% croscarmellose sodium (cross-linked sodium carboxymethyl cellulose)
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was smooth, highly glossy, had a strong color and good opacity. This coating was judged to have a higher gloss than that expected for a conventional thin film-coated tablet core.
Example 3
Using a sample containing the following compound (% by weight)
39.75% Eudolite RS (ammonio methacrylate copolymer)
39.75% Crucell (hydroxypropyl cell sauce)
15.0% titanium dioxide
5.0% aluminum rake
0.5% Aerosil 200 (colloidal silicon dioxide)
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was smooth, glossy, had a strong color and good opacity.
Example 4
Using a sample containing the following compound (% by weight)
60.0% Eudolite RS (ammonio methacrylate copolymer)
20.0% Glycerol monostearate
15.0% titanium dioxide
5.0% aluminum rake
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was smooth, matte, had a strong color and good opacity.
Example 5
Using a sample containing the following compound (% by weight)
60.0% Eudolite RS (ammonio methacrylate copolymer)
20.0% Xylitol
15.0% titanium dioxide
5.0% aluminum rake
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was semi-gloss, had a strong color and good opacity.
Example 6
Using a sample containing the following compound (% by weight)
46.5% Eudolite RS (ammonio methacrylate copolymer)
28.0% Crucell (hydroxypropyl cell sauce)
15.0% titanium dioxide
5.0% aluminum rake
5.0% polyethylene glycol 6000
0.5% Aerosil 200 (colloidal silicon dioxide)
A powder coating material was prepared by the method described in steps (a) to (d) of Example 1. As described in step (e) of Example 1, the powder material was applied to the tablet core surface and melted. The resulting coating was smooth, had a strong color and good opacity.
Example 7
A sample containing the following compound (% by weight)
56.25% polyethylene glycol
20.0% Titanium dioxide
18.75% Eudolite RS (ammonio methacrylate copolymer)
5.0% aluminum rake
Formulated using a high shear mixer. In the pre-formulation state, polyethylene glycol and eudolite are at least 50% by volume of particles having a size of 100-200 μm and similar particle sizes, and at least 50% by volume of titanium dioxide and aluminum lake are less than 1 μm. Had a size.
(B) The dried blended mixture was pulverized to obtain a powder material having a particle size of 300 μm or less in which at least 50% by volume of the particles had a size of 100 to 200 μm.
(C) The material was applied to the tablet core using the method and apparatus described above, including a pretreatment spray of polyethylene glycol. The coating powder on the tablet core was heated to a temperature of about 130 ° C. for about 5 seconds using an infrared source to melt the powder coating on the tablet core surface. The resulting coating was smooth, high gloss, strong color and good opacity. This coating was judged to have a higher gloss than that expected for a conventional thin film-coated tablet core.
Example 8
A sample containing the following compound (% by weight)
56.25% polyethylene glycol
20.0% Titanium dioxide
18.75% Eudolite RS (ammonio methacrylate copolymer)
5.0% aluminum rake
Dry blended using a high shear mixer and the blended mixture was milled as described in Example 7, step (b). In addition, the said component had the particle size similar to the particle size as described in Example 7 before the preparation (polyethylene glycol has the same particle size as that of Udrite). The resulting material was applied to the tablet core as described in step (c) of Example 7. The resulting coating was smooth, high gloss, strong color and good opacity. This coating was judged to have a higher gloss than that expected for a conventional thin film-coated tablet core.
In the above embodiment, all the components are in the form of a particulate solid material, but the powder coating material may contain a liquid-shaped component.

Claims (39)

粉末材料で医薬基材を静電塗装する方法であって、粉末材料は医薬的に容認でき、複合粒子を含有し、各複合粒子は、異なる物理的及び／又は化学的特性を有する第１成分及び第２成分を少なくとも含み、
前記第１成分は、２５０℃以下の温度で溶融して基材表面に連続薄膜を形成し、ポリオキシエチレン、糖アルコール、不飽和または飽和脂肪酸またはそのエステル、セルロース誘導体、ポリエチレングリコール、ワックスまたはオイル、ワックスまたはオイルのアルコール、ポロクサマー、アルキルフタレート、クエン酸またはそのエステルから成る群から選択される１以上の化合物を含み、
前記第２成分は、粉末材料に静電気特性を付与し、アクリル酸、アクリル酸のポリマーとコポリマーおよびその誘導体、ポリアルケンとその誘導体、ポリビニルアルコールとエステル、セルロースとその誘導体、ポリラクチド、ポリグリコリド、ポリヒドロキシブチレート、ポリヒドロキシバレレート、エチレンビニルアセテートコポリマー、ポリ酸無水物、ポリエチレンオキシドから成る群から選択される１以上の化合物を含み、
基材を前記粉末材料で被覆した後、前記粉末材料を溶融し、基材に固定した連続薄膜を形成する、前記方法。A method of electrostatically coating a pharmaceutical substrate with a powder material, wherein the powder material is pharmaceutically acceptable and contains composite particles, each composite particle having a first component having different physical and / or chemical properties And at least a second component,
The first component is melted at a temperature of 250 ° C. or lower to form a continuous thin film on the surface of the substrate, and polyoxyethylene, sugar alcohol, unsaturated or saturated fatty acid or ester thereof, cellulose derivative, polyethylene glycol, wax or oil. One or more compounds selected from the group consisting of alcohols of waxes or oils, poloxamers, alkyl phthalates, citric acid or esters thereof,
The second component imparts electrostatic properties to the powder material, and includes acrylic acid, polymers and copolymers of acrylic acid and derivatives thereof, polyalkene and derivatives thereof, polyvinyl alcohol and esters, cellulose and derivatives thereof, polylactide, polyglycolide, polyhydroxy Including one or more compounds selected from the group consisting of butyrate, polyhydroxyvalerate, ethylene vinyl acetate copolymer, polyanhydride, polyethylene oxide,
The method, wherein after coating a base material with the powder material, the powder material is melted to form a continuous thin film fixed to the base material. 前記材料の粒子の少なくとも５０重量％が複合粒子である、請求項１に記載する方法。The method of claim 1, wherein at least 50% by weight of the material particles are composite particles. 全ての粒子が複合粒子である請求項２に記載の方法。The method of claim 2, wherein all particles are composite particles. 粉末の粒子の少なくとも３０容量％が、５μｍ〜２５μｍの範囲の粒子サイズを有する、請求項１から３のいずれか一項に記載する方法。4. A method according to any one of claims 1 to 3, wherein at least 30% by volume of the particles of the powder have a particle size in the range of 5 [mu] m to 25 [mu] m. 少なくとも９０容量％の材料の粒子が、５０μｍ以下の粒子サイズを有する、請求項１から４のいずれか一項に記載する方法。5. A method according to any one of the preceding claims, wherein the particles of at least 90% by volume of material have a particle size of 50 [mu] m or less. 少なくとも５０容量％の材料の粒子が、少なくとも５μｍの粒子サイズを有する、請求項１から５のいずれか一項に記載する方法。6. A method according to any one of the preceding claims, wherein the particles of at least 50% by volume of material have a particle size of at least 5 [mu] m. 第１成分が、セルロース誘導体、ポリオキシエチレン、ポリエチレングリコール、脂肪酸またはそのエステル、または２以上のこれらの化合物を含む請求項１から６のいずれか一項に記載する方法。The method according to any one of claims 1 to 6, wherein the first component comprises a cellulose derivative, polyoxyethylene, polyethylene glycol, a fatty acid or an ester thereof, or two or more of these compounds. 材料がその重量に基づき、少なくとも１０重量％の第１成分を含有する請求項１から７のいずれか一項に記載する方法。8. A method according to any one of the preceding claims, wherein the material contains at least 10% by weight of the first component, based on its weight. 第２成分が、アクリル酸の誘導体のポリマーまたはコポリマー、ポリビニルエステルまたはポリエチレンオキシドまたは２以上のこれらの化合物を含む請求項１から８のいずれか一項に記載する方法。9. A method according to any one of claims 1 to 8, wherein the second component comprises a polymer or copolymer of a derivative of acrylic acid, a polyvinyl ester or polyethylene oxide or two or more of these compounds. 材料がその重量に基づき、少なくとも１０重量％の第２成分を含有する、請求項１から９のいずれか一項に記載する方法。10. A method according to any one of the preceding claims, wherein the material contains at least 10% by weight of the second component, based on its weight. 材料が第１成分と第２成分の分散を改良するための分散剤成分を含む、請求項１から１０のいずれか一項に記載する方法。11. A method according to any one of the preceding claims, wherein the material comprises a dispersant component for improving the dispersion of the first component and the second component. 材料が減摩剤、崩壊剤、不透明化剤、着色剤、風味剤より選ばれる少なくとも１つの成分を含む、請求項１から１１のいずれか一項に記載する方法。12. A method according to any one of the preceding claims, wherein the material comprises at least one component selected from a lubricant, disintegrant, opacifier, colorant, flavor. 材料が１０8〜１０16Ωｍの範囲の固有抵抗を持っている、請求項１から１２のいずれか一項に記載する方法。Material has a resistivity in the range of 10 8 ~10 16 Ωm, a method of any one of claims 1 to 12. 材料が摩擦帯電的に及び／又はコロナ帯電により帯電可能である、請求項１から１３のいずれか一項に記載する方法。14. A method according to any one of the preceding claims, wherein the material can be charged triboelectrically and / or by corona charging. 材料がエレクトレット、磁石または常磁性体である、請求項１から１４のいずれか一項に記載する方法。The method according to any one of claims 1 to 14, wherein the material is an electret, a magnet or a paramagnetic material. 複合粒子が、個々に分離した粒子の形態を有する、請求項１から１５のいずれか一項に記載する方法。16. A method according to any one of claims 1 to 15, wherein the composite particles have the form of individually separated particles. 複合粒子が、異なる成分の個々に分離した粒子の凝集体または集塊の形態を有する、請求項１から１５のいずれか一項に記載する方法。16. A method according to any one of the preceding claims, wherein the composite particles have the form of agglomerates or agglomerates of individually separated particles of different components. 粉末塗装材料が、活性材料を含む、請求項１から１７のいずれか一項に記載する方法。18. A method according to any one of claims 1 to 17, wherein the powder coating material comprises an active material. 粉末塗装材料が中の活性材料は、酸消化・運動誘導剤、緩下剤、制痢剤、結腸・直腸薬、膵臓酵素と胆汁酸、抗不整脈薬、抗狭心症薬、利尿剤、抗高血圧薬、抗凝固薬、抗血栓薬、フィブリン溶解薬、止血薬、脂肪欠乏症薬、抗貧血・好中球減少病薬、催眠薬、抗不安薬、抗精神病薬、抗うつ薬、制吐薬、鎮痙薬、ＣＮＳ刺激薬、鎮痛薬、解熱薬、抗片頭痛薬、非ステロイド性抗炎症薬、抗通風薬、筋弛緩薬、神経筋薬、ステロイド、低血糖症薬、高血糖症薬、診断薬、抗生物質、抗真菌性薬、抗マラリヤ薬、抗ウイルス薬、免疫抑制薬、栄養薬、ビタミン、電解質、食欲抑制剤、欲求抑制剤、気管支拡張薬、去痰薬、鎮咳薬、粘液溶解薬、うつ血除去薬、抗緑内障薬、経口避妊薬、及び／又は抗腫瘍性薬から選択される１またはそれ以上の化合物を含む請求項１８に記載の方法。Active materials in powder coating materials include acid digestion / exercise inducers, laxatives, antidiarrheals, colon and rectal drugs, pancreatic enzymes and bile acids, antiarrhythmic drugs, antianginal drugs, diuretics, antihypertensive drugs , Anticoagulant, antithrombotic, fibrinolytic, hemostatic, fat deficiency, anti-anemic / neutropenia, hypnotic, anxiolytic, antipsychotic, antidepressant, antiemetic, antispasmodic , CNS stimulant, analgesic, antipyretic, anti-migraine, nonsteroidal anti-inflammatory, anti-ventilant, muscle relaxant, neuromuscular, steroid, hypoglycemic, hyperglycemic, diagnostic, Antibiotics, antifungal drugs, antimalarial drugs, antiviral drugs, immunosuppressive drugs, nutritional drugs, vitamins, electrolytes, appetite suppressants, desire suppressants, bronchodilators, expectorants, antitussives, mucolytic drugs, depression One or more selected from blood removal agents, antiglaucoma agents, oral contraceptives, and / or antitumor agents The method of claim 18 comprising the compound. 粉末塗装材料はその重量を基準にして、少なくとも０．５重量％の活性材料を含む、請求項１８または請求項１９に記載の方法。20. A method according to claim 18 or claim 19, wherein the powder coating material comprises at least 0.5% by weight of active material, based on its weight. 被覆された基材は経口摂取される医薬品を構成する、請求項１８から２０のいずれか一項に記載する方法。21. A method according to any one of claims 18 to 20, wherein the coated substrate constitutes an orally ingested pharmaceutical product. 被覆された基材は経口摂取しない医薬品を構成する、請求項１８から２０のいずれか一項に記載する方法。21. A method according to any one of claims 18 to 20, wherein the coated substrate constitutes a medicinal product that is not taken orally. 医薬製品が錠剤、ペレット、カプセル、小球、ペッサリー、ブージー及び座薬からなる群から選択される投与単位を形成する請求項２１または２２に記載する方法。23. A method according to claim 21 or 22, wherein the pharmaceutical product forms a dosage unit selected from the group consisting of tablets, pellets, capsules, globules, pessaries, bougies and suppositories. 基材が錠剤芯である請求項２１に記載する方法。The method according to claim 21, wherein the substrate is a tablet core. 医薬基材が粉末材料とは異なる活性材料を含む、請求項１８から２４のいずれか一項に記載の方法。25. A method according to any one of claims 18 to 24, wherein the pharmaceutical substrate comprises an active material that is different from the powder material. 医薬基材が活性材料を含まない、請求項１８から２４のいずれか一項に記載の方法。25. A method according to any one of claims 18 to 24, wherein the pharmaceutical substrate does not comprise an active material. 医薬基材が粉末塗装材料と同じ活性材料を含む、請求項１８から２４のいずれか一項に記載の方法。25. A method according to any one of claims 18 to 24, wherein the pharmaceutical substrate comprises the same active material as the powder coating material. 基材が経口摂取される医薬製品である、請求項１から１７のいずれか一項に記載の方法。18. A method according to any one of claims 1 to 17, wherein the substrate is a pharmaceutical product that is taken orally. 基材を粉末塗装材料供給源に近接して保持し、基材表面を塗装材料の電位と異なる電位に維持して、電位の適用により粉末を粉末供給源から基材に向けて移動させ、そして基材表面を粉末塗装材料で塗装する、請求項１から２８のいずれか一項に記載する方法。Holding the substrate in close proximity to the powder coating material source, maintaining the substrate surface at a potential different from that of the coating material, applying the potential to move the powder from the powder source toward the substrate; and The method according to any one of claims 1 to 28, wherein the substrate surface is coated with a powder coating material. 基材が粉末塗装材料供給源に近接するときに、基材を帯電させる、請求項２９に記載する方法。30. The method of claim 29, wherein the substrate is charged when the substrate is proximate to the powder coating material source. 粉末塗装材料供給源が接地されている、請求項３０に記載する方法。32. The method of claim 30, wherein the powder coating material source is grounded. 基材が上方に保持され、粉末が供給源から上方に基材下部表面に向けて移動する、請求項２９から３１のいずれか一項に記載する方法。32. A method according to any one of claims 29 to 31 wherein the substrate is held upward and the powder moves upward from the source towards the substrate lower surface. 基材を粉末塗装材料供給源に近接して保持する前に、基材表面に前処理組成物を適用する、請求項２９から３２のいずれか一項に記載する方法。33. A method according to any one of claims 29 to 32, wherein the pretreatment composition is applied to the substrate surface prior to holding the substrate in proximity to the powder coating material source. 塗装した基材を粉末塗装材料供給源に近接して保持し、基材の未塗装面を露出させ且つ基材表面を塗装材料の電位と異なる電位に維持して、電位の適用により粉末を粉末供給源から基材に向けて移動させ、基材の露出表面を粉末塗装材料で塗装する工程をさらに含む、請求項２９から３３のいずれか一項に記載する方法。Hold the painted substrate close to the powder coating material supply source, expose the unpainted surface of the substrate and maintain the substrate surface at a potential different from the potential of the coating material, and apply the potential to powder the powder 34. A method according to any one of claims 29 to 33, further comprising moving from a source toward the substrate and painting the exposed surface of the substrate with a powder coating material. 医薬的に容認でき、処理により薄膜塗装を形成でき、且つ複合粒子を含み、各複合粒子は、異なる物理的及び／又は化学的特性を有する第１成分及び第２成分を少なくとも含み、
前記第１成分は、２５０℃以下の温度で溶融して基材表面に連続薄膜を形成し、ポリオキシエチレン、糖アルコール、不飽和または飽和脂肪酸またはそのエステル、セルロース誘導体、ポリエチレングリコール、ワックスまたはオイル、ワックスまたはオイルのアルコール、ポロクサマー、アルキルフタレート、クエン酸またはそのエステルから成る群から選択される１以上の化合物を含み、
前記第２成分は、粉末材料に静電気特性を付与し、アクリル酸、アクリル酸のポリマーとコポリマーおよびその誘導体、ポリアルケンとその誘導体、ポリビニルアルコールとエステル、セルロースとその誘導体、ポリラクチド、ポリグリコリド、ポリヒドロキシブチレート、ポリヒドロキシバレレート、エチレンビニルアセテートコポリマー、ポリ酸無水物、ポリエチレンオキシドから成る群から選択される１以上の化合物を含み、
粉末の粒子の少なくとも３０容量％が５μｍ〜２５μｍの範囲の粒子サイズを有する粉末塗装材料の医薬基材静電塗装における使用。 Medical drug to unacceptable treatment by can form a thin film coating and includes composite particles, each composite particle comprises at least a first component and a second component having different physical and / or chemical properties,
The first component is melted at a temperature of 250 ° C. or lower to form a continuous thin film on the surface of the substrate, and polyoxyethylene, sugar alcohol, unsaturated or saturated fatty acid or ester thereof, cellulose derivative, polyethylene glycol, wax or oil. One or more compounds selected from the group consisting of alcohols of waxes or oils, poloxamers, alkyl phthalates, citric acid or esters thereof,
The second component imparts electrostatic properties to the powder material, and includes acrylic acid, polymers and copolymers of acrylic acid and derivatives thereof, polyalkene and derivatives thereof, polyvinyl alcohol and esters, cellulose and derivatives thereof, polylactide, polyglycolide, polyhydroxy Including one or more compounds selected from the group consisting of butyrate, polyhydroxyvalerate, ethylene vinyl acetate copolymer, polyanhydride, polyethylene oxide,
Use of a powder coating material in a pharmaceutical substrate electrostatic coating, wherein at least 30% by volume of the particles of the powder have a particle size in the range of 5 to 25 μm. 塗装材料が請求項２から２２のいずれかに特定したものである、請求項３５に記載の使用。36. Use according to claim 35, wherein the coating material is as specified in any of claims 2 to 22. 医薬的に容認でき、処理により薄膜塗装を形成でき、且つ複合粒子を含み、各複合粒子は、異なる物理的及び／又は化学的特性を有する第１成分及び第２成分を少なくとも含み、
前記第１成分は、２５０℃以下の温度で溶融して基材表面に連続薄膜を形成し、ポリオキシエチレン、糖アルコール、不飽和または飽和脂肪酸またはそのエステル、セルロース誘導体、ポリエチレングリコール、ワックスまたはオイル、ワックスまたはオイルのアルコール、ポロクサマー、アルキルフタレート、クエン酸またはそのエステルから成る群から選択される１以上の化合物を含み、
前記第２成分は、粉末材料に静電気特性を付与し、アクリル酸、アクリル酸のポリマーとコポリマーおよびその誘導体、ポリアルケンとその誘導体、ポリビニルアルコールとエステル、セルロースとその誘導体、ポリラクチド、ポリグリコリド、ポリヒドロキシブチレート、ポリヒドロキシバレレート、エチレンビニルアセテートコポリマー、ポリ酸無水物、ポリエチレンオキシドから成る群から選択される１以上の化合物を含み、
前記材料が活性材料をも含む粉末塗装材料の医薬基材の静電塗装における使用。 Medical drug to unacceptable treatment by can form a thin film coating and includes composite particles, each composite particle comprises at least a first component and a second component having different physical and / or chemical properties,
The first component is melted at a temperature of 250 ° C. or lower to form a continuous thin film on the surface of the substrate, and polyoxyethylene, sugar alcohol, unsaturated or saturated fatty acid or ester thereof, cellulose derivative, polyethylene glycol, wax or oil. One or more compounds selected from the group consisting of alcohols of waxes or oils, poloxamers, alkyl phthalates, citric acid or esters thereof,
The second component imparts electrostatic properties to the powder material, and includes acrylic acid, polymers and copolymers of acrylic acid and derivatives thereof, polyalkene and derivatives thereof, polyvinyl alcohol and esters, cellulose and derivatives thereof, polylactide, polyglycolide, polyhydroxy Including one or more compounds selected from the group consisting of butyrate, polyhydroxyvalerate, ethylene vinyl acetate copolymer, polyanhydride, polyethylene oxide,
Use of a powder coating material in which the material also comprises an active material in electrostatic coating of a pharmaceutical substrate . 塗装材料が請求項１９−２２に基づくものである、請求項３７に記載の使用。Coating material is based on claims 19-22, use as claimed in claim 37. 基材が経口摂取される医薬製品である、請求項３５から３８のいずれか一項に記載の使用。 39. Use according to any one of claims 35 to 38 , wherein the substrate is a pharmaceutical product that is taken orally.
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